<PAGE>   1
  As filed with the Securities and Exchange Commission on May 27, 1999

                                                Registration No. 333-___________
================================================================================

                       SECURITIES AND EXCHANGE COMMISSION
                              Washington, DC 20549

                                 -------------

                                    FORM S-8
                             REGISTRATION STATEMENT
                                      UNDER
                           THE SECURITIES ACT OF 1933

                                 -------------

                       LIGAND PHARMACEUTICALS INCORPORATED
             (Exact name of registrant as specified in its charter)

              DELAWARE
  (State or other jurisdiction                            77-0160744
of incorporation or organization)              (IRS Employer Identification No.)

                           10275 SCIENCE CENTER DRIVE
                           SAN DIEGO, CALIFORNIA 92121
               (Address of principal executive offices) (Zip Code)

                                 -------------

                      1992 STOCK OPTION/STOCK ISSUANCE PLAN
                        1992 EMPLOYEE STOCK PURCHASE PLAN
                            (Full title of the plans)

                                 -------------

                                DAVID E. ROBINSON
                      PRESIDENT AND CHIEF EXECUTIVE OFFICER
                       LIGAND PHARMACEUTICALS INCORPORATED
             10275 SCIENCE CENTER DRIVE, SAN DIEGO, CALIFORNIA 92121
                     (Name and address of agent for service)
                                 (619) 535-3900
          (Telephone number, including area code, of agent for service)

                                 -------------

<TABLE>
<CAPTION>
                                 CALCULATION OF REGISTRATION FEE
=============================================================================================================
                                                               Proposed        Proposed
                 Title of                                       Maximum         Maximum
                Securities                      Amount         Offering        Aggregate        Amount of
                  to be                          to be           Price         Offering       Registration
                Registered                   Registered(1)     per Share         Price             Fee
-------------------------------------------------------------------------------------------------------------
<S>                                        <C>                 <C>             <C>              <C>
1992 Stock Option/
Stock Issuance Plan

Common Stock, par value $0.001             985,000 shares      10.875(2)       10,711,875(2)    $2,977.90
1992 Employee Stock
Purchase Plan

Common Stock, par value $0.001              95,000 shares      10.875(2)       1,033,125(2)     $  287.21

Aggregate Amount of Registration Fee                                                            $3,265.11
=============================================================================================================
</TABLE>

(1)  This Registration Statement shall also cover any additional shares of
     registrant's Common Stock which become issuable under the 1992 Stock
     Option/Stock Issuance Plan and the 1992 Employee Stock Purchase Plan, or
     which become issuable to the Selling Stockholders, by reason of any stock
     dividend, stock split, recapitalization or other similar transaction
     effected without our receipt of consideration and which results in an
     increase in the number of our outstanding shares of Common Stock.

(2)  Calculated solely for purposes of this offering under Rule 457(h) and
     457(c) of the Securities Act of 1933, as amended, on the basis of the
     average of the high and low selling prices per share of registrant's Common
     Stock on May 24, 1999, as reported by the Nasdaq National Market.

================================================================================

<PAGE>   2

                       WHERE YOU CAN FIND MORE INFORMATION

        We file annual, quarterly and special reports, proxy statements and
other information with the SEC. You may read and copy any document we have on
file at the SEC's public reference rooms in Washington, DC, New York, New York
and Chicago, Illinois. Please call the SEC at 1-800-SEC-0300 for further
information about the public reference rooms. Our SEC filings are also available
to the public at the SEC's web site at http://www.sec.gov.


                                     PART II

               INFORMATION REQUIRED IN THE REGISTRATION STATEMENT

ITEM 3. INCORPORATION OF DOCUMENTS BY REFERENCE

        The SEC allows us to "incorporate by reference" the information we file
with them, which means that we can disclose important information to you by
referring you to those documents. The information incorporated by reference is
considered to be part of this registration statement, and later information
filed with the SEC will update and supersede this information. We incorporate by
reference the documents listed below and any future filings made with the SEC
under Sections 13(a), 13(c), 14 or 15(d) of the Securities Exchange Act of 1934
until our offering is complete:

        (a)   Our Annual Report on Form 10-K for the fiscal year ended December
              31, 1998, filed on March 31, 1999;

        (b)   Our Quarterly Report on Form 10-Q for the quarter ended March 31,
              1999, filed on May 15, 1999;

        (c)   The description of our Common Stock, par value 0.001 per share,
              contained in our Form 8-A registration statement, filed on
              November 21, 1994;

        (d)   Our Amended and Restated Certificate of Incorporation, filed on
              July 9, 1998, as Exhibit 3.2 to our Form S-4 registration
              statement;

        (e)   Our Bylaws, filed on July 9, 1998, as Exhibit 3.3 to our Form S-4
              registration statement;

        (f)   Our Form of Stock Option Agreement filed on April 16, 1992, as
              Exhibit 10.2 to our Form S-1 registration statement;

        (g)   Our Form of Stock Issuance Agreement filed on April 16, 1992, as
              Exhibit 10.3 to our Form S-1 registration statement; and

        (h)   Our Form of Stock Purchase Agreement filed on April 16, 1992, as
              Exhibit 10.13 to our Form S-1 registration statement.

        All reports and other documents that we subsequently filed under
Sections 13(a), 13(c), 14 and 15(d) of the Securities Exchange Act of 1934, as
amended (the "1934 Act"), prior to the filing of a post-effective amendment
which indicates that all securities offered under this registration statement
have been sold or which deregisters all securities then remaining unsold, shall
be deemed to be incorporated by reference into this registration statement and
to be a part of this registration statement from the date of filing of such
documents. Any statement contained in a document incorporated or deemed to be
incorporated by reference into this registration statement shall be deemed to be
modified or superseded for purposes of this registration statement to the extent
that a statement contained in this registration statement or in any subsequently
filed document which also is deemed to be incorporated by reference in this
registration statement modifies or supersedes such statement. Any such statement
so modified or superseded shall not be deemed, except as so modified or
superseded, to constitute a part of this registration statement.





                                      II-1

<PAGE>   3



        You may request a copy of these filings, at no cost, by writing or
telephoning us at the following address:

        Ligand Pharmaceuticals Incorporated
        10275 Science Center Drive
        San Diego, California  92121
        Attn:  Secretary
        (619) 535-3900

ITEM 4. DESCRIPTION OF SECURITIES

        Not Applicable.

ITEM 5. INTERESTS OF NAMED EXPERTS AND COUNSEL

        Not Applicable.

ITEM 6. INDEMNIFICATION OF DIRECTORS AND OFFICERS

        (a) Section 145 of the Delaware General Corporation Law permits
indemnification of our officers and directors under certain conditions and
subject to certain limitations. Section 145 of the Delaware General Corporation
Law also provides that a corporation has the power to purchase and maintain
insurance on behalf of its officers and directors against any liability asserted
against such person and incurred by him or her in such capacity, or arising out
of his or her status as such, whether or not the corporation would have the
power to indemnify him or her against such liability under the provisions of
Section 145 of the Delaware General Corporation Law.

        (b) Article VII, Section 1 of our Bylaws provides that we shall
indemnify our officers, directors, employees and agents to the full extent
permitted by the General Corporation Law of Delaware. The rights to indemnity
thereunder continue as to a person who has ceased to be a director, officer,
employee or agent and inure to the benefit of the heirs, executors and
administrators of the person. In addition, expenses incurred by a director or
officer in defending any civil, criminal, administrative or investigative
action, suit or proceeding by reason of the fact that he or she is or was our
director or officer (or was serving at our request as a director or officer of
another corporation) shall be paid by us in advance of the final disposition of
such action, suit or proceeding upon receipt of an undertaking by or on behalf
of such director or officer to repay such amount if it shall ultimately be
determined that he or she is not entitled to be indemnified by us as authorized
by the relevant section of the Delaware General Corporation Law.

        (c) As permitted by Section 102(b)(7) of the Delaware General
Corporation Law, Article VI, Section (A)2 of our Amended and Restated
Certificate of Incorporation provides that our directors shall not be personally
liable for monetary damages or breach of fiduciary duty as a director, except
for liability for (i) any breach of the director's duty of loyalty to us or our
stockholders, (ii) acts or omissions not in good faith or which involve
intentional misconduct or a knowing violation of law, (iii) unlawful payment of
dividends or unlawful stock purchases or redemptions under Section 174 of the
Delaware General Corporation Law, or (iv) any transaction from which the
director derived any improper personal benefit.

        (d) Pursuant to authorization provided under the Amended and Restated
Certificate of Incorporation, we have entered into indemnification agreements
with each of our present and certain of our former directors. We have also
entered into similar agreements with certain of our executive officers who are
not directors. Generally, the indemnification agreements attempt to provide the
maximum protection permitted by Delaware and California law as it may be amended
from time to time. Moreover, the indemnification agreements provide for certain
additional indemnification.

        (e) We now have in effect directors and officers liability insurance
which insures our directors and officers.

ITEM 7. EXEMPTION FROM REGISTRATION CLAIMED

        Not Applicable.





                                      II-2
<PAGE>   4


ITEM 8. EXHIBITS

<TABLE>
<CAPTION>

        Exhibit Number      Exhibit
        --------------      -------
             <S>            <C>
              4.1           Instruments defining the rights of stockholders.
                            Reference is made to our Form 8-A registration
                            statement filed on November 21, 1994 (incorporated
                            into this registration statement by reference), the
                            Amended and Restated Certificate of Incorporation
                            (incorporated into this registration statement by
                            reference to Exhibit 3.2 to our Form S-4
                            registration statement filed on July 9, 1998) and
                            the Bylaws (incorporated into this registration
                            statement by reference to Exhibit 3.3 of our Form
                            S-4 registration statement, filed on July 9, 1998).

              5.1           Opinion and Consent of Brobeck, Phleger & Harrison
                            LLP.

             23.1           Consent of Brobeck, Phleger & Harrison LLP
                            (contained in Exhibit 5.1).

             23.2           Consent of Ernst & Young LLP, independent auditors.

             24.1           Power of Attorney. Reference is made to page II-4 of
                            this registration statement.

             99.1           1992 Stock Option/Stock Issuance Plan (as amended
                            May 20, 1999).

             99.2           Form of Stock Option Agreement. Reference is made to
                            Exhibit 10.2 to our Form S-1 registration statement,
                            filed on April 16, 1992, which is incorporated into
                            this registration statement by reference.

             99.3           Form of Stock Issuance Agreement. Reference is made
                            to Exhibit 10.3 to our Form S-1 registration
                            statement, filed on April 16, 1992, which is
                            incorporated into this registration statement by
                            reference.

             99.4           1992 Employee Stock Purchase Plan (as amended May
                            20, 1999).

             99.5           Form of Stock Purchase Agreement. Reference is made
                            to Exhibit 10.13 to our Form S-1 registration
                            statement, filed on April 16, 1992, which is
                            incorporated into this registration statement by
                            reference.
</TABLE>





                                      II-3
<PAGE>   5


ITEM 9. UNDERTAKINGS

        A. The undersigned registrant hereby undertakes: (1) to file, during any
period in which offers or sales are being made, a post-effective amendment to
this registration statement (i) to include any prospectus required by Section
10(a)(3) of the 1933 Act, (ii) to reflect in the prospectus any facts or events
arising after the effective date of this Registration Statement (or the most
recent post-effective amendment thereof) which, individually or in the
aggregate, represent a fundamental change in the information set forth in this
Registration Statement and (iii) to include any material information with
respect to the plan of distribution not previously disclosed in this
Registration Statement or any material change to such information in this
Registration Statement; provided, however, that clauses (1)(i) and (1)(ii) shall
not apply if the information required to be included in a post-effective
amendment by those clauses is contained in periodic reports filed by the
registrant pursuant to Section 13 or Section 15(d) of the 1934 Act that are
incorporated by reference into this Registration Statement; (2) that for the
purpose of determining any liability under the 1933 Act, each such
post-effective amendment shall be deemed to be new registration statement
relating to the securities offered therein, and the offering of such securities
at that time shall be deemed to be the initial bona fide offering thereof; and
(3) to remove from registration by means of a post-effective amendment any of
the securities being registered which remain unsold at the termination of the
offering.

        B. The undersigned registrant hereby undertakes that, for purposes of
determining any liability under the 1933 Act, each filing of our annual report
pursuant to Section 13(a) or Section 15(d) of the 1934 Act that is incorporated
by reference into this Registration Statement shall be deemed to be a new
registration statement relating to the securities offered therein, and the
offering of such securities at that time shall be deemed to be the initial bona
fide offering thereof.

        C. The undersigned registrant hereby undertakes to deliver or cause to
be delivered with the prospectus, to each person to whom the prospectus is sent
or given, the latest annual report, to security holders that is incorporated by
reference in the prospectus and furnished pursuant to and meeting the
requirements of Rule 14a-3 or Rule 14c-3 under the 1934 Act; and, where interim
financial information required to be presented by Article 3 of Regulation S-X is
not set forth in the prospectus, to deliver, or cause to be delivered to each
person to whom the prospectus is sent or given, the latest quarterly report that
is specifically incorporated by reference in the prospectus to provide such
interim financial information.

        D. Insofar as indemnification for liabilities arising under the 1933 Act
may be permitted to directors, officers, or controlling persons of the
registrant pursuant to the indemnification provisions summarized in Item 6 above
or otherwise, the registrant has been advised that, in the opinion of the SEC,
such indemnification is against public policy as expressed in the 1933 Act, and
is, therefore, unenforceable. In the event that a claim for indemnification
against such liabilities (other than the payment by the registrant of expenses
incurred or paid by a director, officer, or controlling person of the registrant
in the successful defense of any action, suit or proceeding) is asserted by such
director, officer or controlling person in connection with the securities being
registered, the registrant will, unless in the opinion of its counsel the matter
has been settled by controlling precedent, submit to a court of appropriate
jurisdiction the question whether such indemnification by it is against public
policy as expressed in the 1933 Act and will be governed by the final
adjudication of such issue.





                                      II-4

<PAGE>   6


                                   SIGNATURES

        Pursuant to the requirements of the Securities Act of 1933, as amended,
the registrant certifies that it has reasonable grounds to believe that it meets
all of the requirements for filing on Form S-8 and has duly caused this
Registration Statement to be signed on its behalf by the undersigned, thereunto
duly authorized, in the City of San Diego, State of California, on this 27th day
of May, 1999.


                                       LIGAND PHARMACEUTICALS INCORPORATED


                                       By: /S/ DAVID E. ROBINSON
                                           _____________________________________
                                           David E. Robinson
                                           President and Chief Executive Officer


                                POWER OF ATTORNEY

                       KNOW ALL PERSONS BY THESE PRESENTS:

        That the undersigned officers and directors of Ligand Pharmaceuticals
Incorporated, a Delaware corporation, do hereby constitute and appoint David E.
Robinson and Paul V. Maier, and each of them, the lawful attorneys-in-fact and
agents with full power and authority to do any and all acts and things and to
execute any and all instruments which said attorneys and agents, and either one
of them, determine may be necessary or advisable or required to enable said
corporation to comply with the Securities Act of 1933, as amended, and any rules
or regulations or requirements of the Securities and Exchange Commission in
connection with this registration statement. Without limiting the generality of
the foregoing power and authority, the powers granted include the power and
authority to sign the names of the undersigned officers and directors in the
capacities indicated below to this registration statement, to any and all
amendments, both pre-effective and post-effective, and supplements to this
registration statement, and to any and all instruments or documents filed as
part of or in conjunction with this registration statement or amendments or
supplements thereof, and each of the undersigned hereby ratifies and confirms
that all said attorneys and agents, or either of them, shall do or cause to be
done by virtue hereof. This Power of Attorney may be signed in several
counterparts.

        Pursuant to the requirements of the Securities Act of 1933, as amended,
this registration statement has been signed below by the following persons in
the capacities and on the dates indicated.

<TABLE>
<CAPTION>
          Signature                             Title                             Date
          ---------                             -----                             ----
<S>                               <C>                                        <C>

/S/ DAVID E. ROBINSON
_____________________________     President, Chief Executive Officer and     May 26, 1999
David E. Robinson                 Director (Principal Executive Officer)

/S/ PAUL V. MAIER
_____________________________     Senior Vice President and Chief            May 21, 1999
Paul V. Maier                     Financial Officer (Principal Financial
                                  and Accounting Officer)

/S/ HENRY F. BLISSENBACH
_____________________________     Director                                   May 26, 1999
Henry F. Blissenbach

/S/ ALEXANDER D. CROSS
_____________________________     Director                                   May 26, 1999
Alexander D. Cross

/S/ MICHAEL A. ROCCA
_____________________________     Director                                   May 18, 1999
Michael A. Rocca

/S/ JOHN GROOM
_____________________________     Director                                   May 20, 1999
John Groom

/S/ IRVING S. JOHNSON, PH.D.
_____________________________     Director                                   May 19, 1999
Irving S. Johnson, Ph.D.

/S/ CARL C. PECK
_____________________________     Director                                   May 21, 1999
Carl C. Peck
</TABLE>





                                      II-5

<PAGE>   7










                       SECURITIES AND EXCHANGE COMMISSION

                                 WASHINGTON, DC

                                    EXHIBITS

                                       TO

                                    FORM S-8

                                      UNDER

                             SECURITIES ACT OF 1933


                       LIGAND PHARMACEUTICALS INCORPORATED



<PAGE>   8


                                  EXHIBIT INDEX

<TABLE>
<CAPTION>
Exhibit Number      Exhibit
--------------      -------
      <S>           <C>
      4.1           Instruments defining the rights of stockholders. Reference
                    is made to our Form 8-A registration statement filed on
                    November 21, 1994 (incorporated into this registration
                    statement by reference), the Amended and Restated
                    Certificate of Incorporation (incorporated into this
                    registration statement by reference to Exhibit 3.2 to our
                    Form S-4 registration statement filed on July 9, 1998) and
                    the Bylaws (incorporated into this registration statement by
                    reference to Exhibit 3.3 of our Form S-4 registration
                    statement, filed on July 9, 1998).

      5.1           Opinion and Consent of Brobeck, Phleger & Harrison LLP.

     23.1           Consent of Brobeck, Phleger & Harrison LLP (contained in
                    Exhibit 5.1).

     23.2           Consent of Ernst & Young LLP, independent auditors.

     24.1           Power of Attorney. Reference is made to page II-4 of this
                    registration statement.

     99.1           1992 Stock Option/Stock Issuance Plan (as amended May 20,
                    1999).

     99.2           Form of Stock Option Agreement. Reference is made to Exhibit
                    10.2 to our Form S-1 registration statement, filed on April
                    16, 1992, which is incorporated into this registration
                    statement by reference.

     99.3           Form of Stock Issuance Agreement. Reference is made to
                    Exhibit 10.3 to our Form S-1 registration statement, filed
                    on April 16, 1992, which is incorporated into this
                    registration statement by reference.

     99.4           1992 Employee Stock Purchase Plan (as amended May 20, 1999).

     99.5           Form of Stock Purchase Agreement. Reference is made to
                    Exhibit 10.13 to our Form S-1 registration statement, filed
                    on April 16, 1992, which is incorporated into this
                    registration statement by reference.
</TABLE>
[{"type": "S-8", "sequence": "1", "description": "FORM S-8", "secsgml_size_bytes": 25245}]
{"company-data": {"conformed-name": "LIGAND PHARMACEUTICALS INC", "cik": "0000886163", "assigned-sic": "2834", "irs-number": "770160744", "state-of-incorporation": "DE", "fiscal-year-end": "1231"}, "filing-values": {"form-type": "S-8", "act": "33", "file-number": "333-79447", "film-number": "99636144"}, "business-address": {"street1": "10275 SCIENCE CENTER DRIVE", "city": "SAN DIEGO", "state": "CA", "zip": "92121-1117", "phone": "6195353900"}, "mail-address": {"street1": "10275 SCIENCE CENTER DRIVE", "city": "SAN DIEGO", "state": "CA", "zip": "92121-1117"}}
1
  As filed with the Securities and Exchange Commission on May 27, 1999

                                                Registration No. 333-___________
================================================================================

                       SECURITIES AND EXCHANGE COMMISSION
                              Washington, DC 20549

                                 -------------

                                    FORM S-8
                             REGISTRATION STATEMENT
                                      UNDER
                           THE SECURITIES ACT OF 1933

                                 -------------

                       LIGAND PHARMACEUTICALS INCORPORATED
             (Exact name of registrant as specified in its charter)

              DELAWARE
  (State or other jurisdiction                            77-0160744
of incorporation or organization)              (IRS Employer Identification No.)

                           10275 SCIENCE CENTER DRIVE
                           SAN DIEGO, CALIFORNIA 92121
               (Address of principal executive offices) (Zip Code)

                                 -------------

                      1992 STOCK OPTION/STOCK ISSUANCE PLAN
                        1992 EMPLOYEE STOCK PURCHASE PLAN
                            (Full title of the plans)

                                 -------------

                                DAVID E. ROBINSON
                      PRESIDENT AND CHIEF EXECUTIVE OFFICER
                       LIGAND PHARMACEUTICALS INCORPORATED
             10275 SCIENCE CENTER DRIVE, SAN DIEGO, CALIFORNIA 92121
                     (Name and address of agent for service)
                                 (619) 535-3900
          (Telephone number, including area code, of agent for service)

                                 -------------
CALCULATION OF REGISTRATION FEE
=============================================================================================================
                                                               Proposed        Proposed
                 Title of                                       Maximum         Maximum
                Securities                      Amount         Offering        Aggregate        Amount of
                  to be                          to be           Price         Offering       Registration
                Registered                   Registered(1)     per Share         Price             Fee
-------------------------------------------------------------------------------------------------------------
1992 Stock Option/
Stock Issuance Plan

Common Stock, par value $0.001             985,000 shares      10.875(2)       10,711,875(2)    $2,977.90
1992 Employee Stock
Purchase Plan

Common Stock, par value $0.001              95,000 shares      10.875(2)       1,033,125(2)     $  287.21

Aggregate Amount of Registration Fee                                                            $3,265.11
=============================================================================================================
(1)  This Registration Statement shall also cover any additional shares of
     registrant's Common Stock which become issuable under the 1992 Stock
     Option/Stock Issuance Plan and the 1992 Employee Stock Purchase Plan, or
     which become issuable to the Selling Stockholders, by reason of any stock
     dividend, stock split, recapitalization or other similar transaction
     effected without our receipt of consideration and which results in an
     increase in the number of our outstanding shares of Common Stock.

(2)  Calculated solely for purposes of this offering under Rule 457(h) and
     457(c) of the Securities Act of 1933, as amended, on the basis of the
     average of the high and low selling prices per share of registrant's Common
     Stock on May 24, 1999, as reported by the Nasdaq National Market.

================================================================================
2

                       WHERE YOU CAN FIND MORE INFORMATION

        We file annual, quarterly and special reports, proxy statements and
other information with the SEC. You may read and copy any document we have on
file at the SEC's public reference rooms in Washington, DC, New York, New York
and Chicago, Illinois. Please call the SEC at 1-800-SEC-0300 for further
information about the public reference rooms. Our SEC filings are also available
to the public at the SEC's web site at http://www.sec.gov.

                                     PART II

               INFORMATION REQUIRED IN THE REGISTRATION STATEMENT

ITEM 3. INCORPORATION OF DOCUMENTS BY REFERENCE

        The SEC allows us to "incorporate by reference" the information we file
with them, which means that we can disclose important information to you by
referring you to those documents. The information incorporated by reference is
considered to be part of this registration statement, and later information
filed with the SEC will update and supersede this information. We incorporate by
reference the documents listed below and any future filings made with the SEC
under Sections 13(a), 13(c), 14 or 15(d) of the Securities Exchange Act of 1934
until our offering is complete:

        (a)   Our Annual Report on Form 10-K for the fiscal year ended December
              31, 1998, filed on March 31, 1999;

        (b)   Our Quarterly Report on Form 10-Q for the quarter ended March 31,
              1999, filed on May 15, 1999;

        (c)   The description of our Common Stock, par value 0.001 per share,
              contained in our Form 8-A registration statement, filed on
              November 21, 1994;

        (d)   Our Amended and Restated Certificate of Incorporation, filed on
              July 9, 1998, as Exhibit 3.2 to our Form S-4 registration
              statement;

        (e)   Our Bylaws, filed on July 9, 1998, as Exhibit 3.3 to our Form S-4
              registration statement;

        (f)   Our Form of Stock Option Agreement filed on April 16, 1992, as
              Exhibit 10.2 to our Form S-1 registration statement;

        (g)   Our Form of Stock Issuance Agreement filed on April 16, 1992, as
              Exhibit 10.3 to our Form S-1 registration statement; and

        (h)   Our Form of Stock Purchase Agreement filed on April 16, 1992, as
              Exhibit 10.13 to our Form S-1 registration statement.

        All reports and other documents that we subsequently filed under
Sections 13(a), 13(c), 14 and 15(d) of the Securities Exchange Act of 1934, as
amended (the "1934 Act"), prior to the filing of a post-effective amendment
which indicates that all securities offered under this registration statement
have been sold or which deregisters all securities then remaining unsold, shall
be deemed to be incorporated by reference into this registration statement and
to be a part of this registration statement from the date of filing of such
documents. Any statement contained in a document incorporated or deemed to be
incorporated by reference into this registration statement shall be deemed to be
modified or superseded for purposes of this registration statement to the extent
that a statement contained in this registration statement or in any subsequently
filed document which also is deemed to be incorporated by reference in this
registration statement modifies or supersedes such statement. Any such statement
so modified or superseded shall not be deemed, except as so modified or
superseded, to constitute a part of this registration statement.

                                      II-1
3

        You may request a copy of these filings, at no cost, by writing or
telephoning us at the following address:

        Ligand Pharmaceuticals Incorporated
        10275 Science Center Drive
        San Diego, California  92121
        Attn:  Secretary
        (619) 535-3900

ITEM 4. DESCRIPTION OF SECURITIES

        Not Applicable.

ITEM 5. INTERESTS OF NAMED EXPERTS AND COUNSEL

        Not Applicable.

ITEM 6. INDEMNIFICATION OF DIRECTORS AND OFFICERS

        (a) Section 145 of the Delaware General Corporation Law permits
indemnification of our officers and directors under certain conditions and
subject to certain limitations. Section 145 of the Delaware General Corporation
Law also provides that a corporation has the power to purchase and maintain
insurance on behalf of its officers and directors against any liability asserted
against such person and incurred by him or her in such capacity, or arising out
of his or her status as such, whether or not the corporation would have the
power to indemnify him or her against such liability under the provisions of
Section 145 of the Delaware General Corporation Law.

        (b) Article VII, Section 1 of our Bylaws provides that we shall
indemnify our officers, directors, employees and agents to the full extent
permitted by the General Corporation Law of Delaware. The rights to indemnity
thereunder continue as to a person who has ceased to be a director, officer,
employee or agent and inure to the benefit of the heirs, executors and
administrators of the person. In addition, expenses incurred by a director or
officer in defending any civil, criminal, administrative or investigative
action, suit or proceeding by reason of the fact that he or she is or was our
director or officer (or was serving at our request as a director or officer of
another corporation) shall be paid by us in advance of the final disposition of
such action, suit or proceeding upon receipt of an undertaking by or on behalf
of such director or officer to repay such amount if it shall ultimately be
determined that he or she is not entitled to be indemnified by us as authorized
by the relevant section of the Delaware General Corporation Law.

        (c) As permitted by Section 102(b)(7) of the Delaware General
Corporation Law, Article VI, Section (A)2 of our Amended and Restated
Certificate of Incorporation provides that our directors shall not be personally
liable for monetary damages or breach of fiduciary duty as a director, except
for liability for (i) any breach of the director's duty of loyalty to us or our
stockholders, (ii) acts or omissions not in good faith or which involve
intentional misconduct or a knowing violation of law, (iii) unlawful payment of
dividends or unlawful stock purchases or redemptions under Section 174 of the
Delaware General Corporation Law, or (iv) any transaction from which the
director derived any improper personal benefit.

        (d) Pursuant to authorization provided under the Amended and Restated
Certificate of Incorporation, we have entered into indemnification agreements
with each of our present and certain of our former directors. We have also
entered into similar agreements with certain of our executive officers who are
not directors. Generally, the indemnification agreements attempt to provide the
maximum protection permitted by Delaware and California law as it may be amended
from time to time. Moreover, the indemnification agreements provide for certain
additional indemnification.

        (e) We now have in effect directors and officers liability insurance
which insures our directors and officers.

ITEM 7. EXEMPTION FROM REGISTRATION CLAIMED

        Not Applicable.

                                      II-2
4

ITEM 8. EXHIBITS
Exhibit Number      Exhibit
        --------------      -------
4.1           Instruments defining the rights of stockholders.
                            Reference is made to our Form 8-A registration
                            statement filed on November 21, 1994 (incorporated
                            into this registration statement by reference), the
                            Amended and Restated Certificate of Incorporation
                            (incorporated into this registration statement by
                            reference to Exhibit 3.2 to our Form S-4
                            registration statement filed on July 9, 1998) and
                            the Bylaws (incorporated into this registration
                            statement by reference to Exhibit 3.3 of our Form
                            S-4 registration statement, filed on July 9, 1998).

              5.1           Opinion and Consent of Brobeck, Phleger & Harrison
                            LLP.

             23.1           Consent of Brobeck, Phleger & Harrison LLP
                            (contained in Exhibit 5.1).

             23.2           Consent of Ernst & Young LLP, independent auditors.

             24.1           Power of Attorney. Reference is made to page II-4 of
                            this registration statement.

             99.1           1992 Stock Option/Stock Issuance Plan (as amended
                            May 20, 1999).

             99.2           Form of Stock Option Agreement. Reference is made to
                            Exhibit 10.2 to our Form S-1 registration statement,
                            filed on April 16, 1992, which is incorporated into
                            this registration statement by reference.

             99.3           Form of Stock Issuance Agreement. Reference is made
                            to Exhibit 10.3 to our Form S-1 registration
                            statement, filed on April 16, 1992, which is
                            incorporated into this registration statement by
                            reference.

             99.4           1992 Employee Stock Purchase Plan (as amended May
                            20, 1999).

             99.5           Form of Stock Purchase Agreement. Reference is made
                            to Exhibit 10.13 to our Form S-1 registration
                            statement, filed on April 16, 1992, which is
                            incorporated into this registration statement by
                            reference.
II-3
5

ITEM 9. UNDERTAKINGS

        A. The undersigned registrant hereby undertakes: (1) to file, during any
period in which offers or sales are being made, a post-effective amendment to
this registration statement (i) to include any prospectus required by Section
10(a)(3) of the 1933 Act, (ii) to reflect in the prospectus any facts or events
arising after the effective date of this Registration Statement (or the most
recent post-effective amendment thereof) which, individually or in the
aggregate, represent a fundamental change in the information set forth in this
Registration Statement and (iii) to include any material information with
respect to the plan of distribution not previously disclosed in this
Registration Statement or any material change to such information in this
Registration Statement; provided, however, that clauses (1)(i) and (1)(ii) shall
not apply if the information required to be included in a post-effective
amendment by those clauses is contained in periodic reports filed by the
registrant pursuant to Section 13 or Section 15(d) of the 1934 Act that are
incorporated by reference into this Registration Statement; (2) that for the
purpose of determining any liability under the 1933 Act, each such
post-effective amendment shall be deemed to be new registration statement
relating to the securities offered therein, and the offering of such securities
at that time shall be deemed to be the initial bona fide offering thereof; and
(3) to remove from registration by means of a post-effective amendment any of
the securities being registered which remain unsold at the termination of the
offering.

        B. The undersigned registrant hereby undertakes that, for purposes of
determining any liability under the 1933 Act, each filing of our annual report
pursuant to Section 13(a) or Section 15(d) of the 1934 Act that is incorporated
by reference into this Registration Statement shall be deemed to be a new
registration statement relating to the securities offered therein, and the
offering of such securities at that time shall be deemed to be the initial bona
fide offering thereof.

        C. The undersigned registrant hereby undertakes to deliver or cause to
be delivered with the prospectus, to each person to whom the prospectus is sent
or given, the latest annual report, to security holders that is incorporated by
reference in the prospectus and furnished pursuant to and meeting the
requirements of Rule 14a-3 or Rule 14c-3 under the 1934 Act; and, where interim
financial information required to be presented by Article 3 of Regulation S-X is
not set forth in the prospectus, to deliver, or cause to be delivered to each
person to whom the prospectus is sent or given, the latest quarterly report that
is specifically incorporated by reference in the prospectus to provide such
interim financial information.

        D. Insofar as indemnification for liabilities arising under the 1933 Act
may be permitted to directors, officers, or controlling persons of the
registrant pursuant to the indemnification provisions summarized in Item 6 above
or otherwise, the registrant has been advised that, in the opinion of the SEC,
such indemnification is against public policy as expressed in the 1933 Act, and
is, therefore, unenforceable. In the event that a claim for indemnification
against such liabilities (other than the payment by the registrant of expenses
incurred or paid by a director, officer, or controlling person of the registrant
in the successful defense of any action, suit or proceeding) is asserted by such
director, officer or controlling person in connection with the securities being
registered, the registrant will, unless in the opinion of its counsel the matter
has been settled by controlling precedent, submit to a court of appropriate
jurisdiction the question whether such indemnification by it is against public
policy as expressed in the 1933 Act and will be governed by the final
adjudication of such issue.

                                      II-4
6

                                   SIGNATURES

        Pursuant to the requirements of the Securities Act of 1933, as amended,
the registrant certifies that it has reasonable grounds to believe that it meets
all of the requirements for filing on Form S-8 and has duly caused this
Registration Statement to be signed on its behalf by the undersigned, thereunto
duly authorized, in the City of San Diego, State of California, on this 27th day
of May, 1999.

                                       LIGAND PHARMACEUTICALS INCORPORATED

                                       By: /S/ DAVID E. ROBINSON
                                           _____________________________________
                                           David E. Robinson
                                           President and Chief Executive Officer

                                POWER OF ATTORNEY

                       KNOW ALL PERSONS BY THESE PRESENTS:

        That the undersigned officers and directors of Ligand Pharmaceuticals
Incorporated, a Delaware corporation, do hereby constitute and appoint David E.
Robinson and Paul V. Maier, and each of them, the lawful attorneys-in-fact and
agents with full power and authority to do any and all acts and things and to
execute any and all instruments which said attorneys and agents, and either one
of them, determine may be necessary or advisable or required to enable said
corporation to comply with the Securities Act of 1933, as amended, and any rules
or regulations or requirements of the Securities and Exchange Commission in
connection with this registration statement. Without limiting the generality of
the foregoing power and authority, the powers granted include the power and
authority to sign the names of the undersigned officers and directors in the
capacities indicated below to this registration statement, to any and all
amendments, both pre-effective and post-effective, and supplements to this
registration statement, and to any and all instruments or documents filed as
part of or in conjunction with this registration statement or amendments or
supplements thereof, and each of the undersigned hereby ratifies and confirms
that all said attorneys and agents, or either of them, shall do or cause to be
done by virtue hereof. This Power of Attorney may be signed in several
counterparts.

        Pursuant to the requirements of the Securities Act of 1933, as amended,
this registration statement has been signed below by the following persons in
the capacities and on the dates indicated.
Signature                             Title                             Date
          ---------                             -----                             ----
/S/ DAVID E. ROBINSON
_____________________________     President, Chief Executive Officer and     May 26, 1999
David E. Robinson                 Director (Principal Executive Officer)

/S/ PAUL V. MAIER
_____________________________     Senior Vice President and Chief            May 21, 1999
Paul V. Maier                     Financial Officer (Principal Financial
                                  and Accounting Officer)

/S/ HENRY F. BLISSENBACH
_____________________________     Director                                   May 26, 1999
Henry F. Blissenbach

/S/ ALEXANDER D. CROSS
_____________________________     Director                                   May 26, 1999
Alexander D. Cross

/S/ MICHAEL A. ROCCA
_____________________________     Director                                   May 18, 1999
Michael A. Rocca

/S/ JOHN GROOM
_____________________________     Director                                   May 20, 1999
John Groom

/S/ IRVING S. JOHNSON, PH.D.
_____________________________     Director                                   May 19, 1999
Irving S. Johnson, Ph.D.

/S/ CARL C. PECK
_____________________________     Director                                   May 21, 1999
Carl C. Peck
II-5
7

                       SECURITIES AND EXCHANGE COMMISSION

                                 WASHINGTON, DC

                                    EXHIBITS

                                       TO

                                    FORM S-8

                                      UNDER

                             SECURITIES ACT OF 1933

                       LIGAND PHARMACEUTICALS INCORPORATED
8

                                  EXHIBIT INDEX
Exhibit Number      Exhibit
--------------      -------
4.1           Instruments defining the rights of stockholders. Reference
                    is made to our Form 8-A registration statement filed on
                    November 21, 1994 (incorporated into this registration
                    statement by reference), the Amended and Restated
                    Certificate of Incorporation (incorporated into this
                    registration statement by reference to Exhibit 3.2 to our
                    Form S-4 registration statement filed on July 9, 1998) and
                    the Bylaws (incorporated into this registration statement by
                    reference to Exhibit 3.3 of our Form S-4 registration
                    statement, filed on July 9, 1998).

      5.1           Opinion and Consent of Brobeck, Phleger & Harrison LLP.

     23.1           Consent of Brobeck, Phleger & Harrison LLP (contained in
                    Exhibit 5.1).

     23.2           Consent of Ernst & Young LLP, independent auditors.

     24.1           Power of Attorney. Reference is made to page II-4 of this
                    registration statement.

     99.1           1992 Stock Option/Stock Issuance Plan (as amended May 20,
                    1999).

     99.2           Form of Stock Option Agreement. Reference is made to Exhibit
                    10.2 to our Form S-1 registration statement, filed on April
                    16, 1992, which is incorporated into this registration
                    statement by reference.

     99.3           Form of Stock Issuance Agreement. Reference is made to
                    Exhibit 10.3 to our Form S-1 registration statement, filed
                    on April 16, 1992, which is incorporated into this
                    registration statement by reference.

     99.4           1992 Employee Stock Purchase Plan (as amended May 20, 1999).

     99.5           Form of Stock Purchase Agreement. Reference is made to
                    Exhibit 10.13 to our Form S-1 registration statement, filed
                    on April 16, 1992, which is incorporated into this
                    registration statement by reference.