<PAGE>

  As filed with the Securities and Exchange Commission on April 23, 1997
                                                      File No. 333-________

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

                          SECURITIES AND EXCHANGE COMMISSION
                                Washington, D.C. 20549
                                                      
                                       FORM S-8
                            REGISTRATION STATEMENT UNDER 
                              THE SECURITIES ACT OF 1933

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

                             CUBIST PHARMACEUTICALS, INC.
                (Exact Name of Registrant as Specified in its Charter)


                 DELAWARE                            22-3192085
         (State or Other Jurisdiction of          (I.R.S. Employer 
         Incorporation or Organization)           Identification No.)



                       24 Emily Street, Cambridge, MA 02139
                 (Address of Principal Executive Offices) (Zip Code)

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

                             CUBIST PHARMACEUTICALS, INC.
                     AMENDED AND RESTATED 1993 STOCK OPTION PLAN
                               (Full Title of the Plan)

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

                               Scott M. Rocklage, Ph.D.
                        President and Chief Executive Officer
                             Cubist Pharmaceuticals, Inc.
                                   24 Emily Street
                            Cambridge, Massachusetts 02139
                       (Name and address of Agent for Service)
                                           
                                    (617) 576-1999
             Telephone Number, Including Area Code, of Agent for Service
                                ----------------------
                                      Copies to:

                               Justin P. Morreale, Esq.
                                 Julio E. Vega, Esq.
                              Bingham, Dana & Gould  LLP
                                  150 Federal Street
                                Boston, MA 02110-1726
                                    (617) 951-8000

                           CALCULATION OF REGISTRATION FEE
                                           

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

Title Of Each       Amount        Proposed        Proposed         Amount Of
Class Of            To Be         Maximum          Maximum        Registration
Securities         Registered     Offering        Aggregate             Fee
To Be Registered                  Price          Offering 
                                  Per Share      Price (1)
------------------------------------------------------------------------------
Common Stock, 
$.001 par value    1,500,000         N/A        $8,417,652.91        2,550.80

------------------------------------------------------------------------------
------------------------------------------------------------------------------
(1) The proposed maximum offering price has been estimated pursuant to 
    Rule 457(h) solely for the purpose of calculating the registration fee. 
    It is not known how many shares will be purchased under the Plan or at 
    what price such shares will be purchased. The estimate of the proposed 
    maximum aggregate offering price has been calculated based on (i) the 
    offering of 703,801 shares, being the portion of the shares of Common 
    Stock registered hereby subject to outstanding options under the Plan, at 
    a weighted average exercise price of $2.91 per share, and (ii) the 
    offering of 796,199 shares, being the aggregate number of shares of 
    Common Stock available for issuance upon exercise of stock options to be 
    granted under the Plan, at an exercise price of $8.00 per share, which is 
    the average of the high and low prices of the Registrant's Common Stock 
    as listed on the National Association of Securities Dealers Automated 
    Quotation ("Nasdaq") National Market System on April 21, 1996.



<PAGE>

                                       PART II
                                           
                  INFORMATION REQUIRED IN THE REGISTRATION STATEMENT
                                           

Item 3.  Incorporation of Documents by Reference.

    The following documents filed by Cubist Pharmaceuticals, Inc. (the
"Registrant") with the Securities and Exchange Commission (the "SEC") are hereby
incorporated by reference in this Registration Statement:  (1) the Registrant's
Annual Report on Form 10-K for the fiscal year ended December 31, 1996; (2) all
reports previously filed by the Registrant pursuant to Section 13(a) or 15(d) of
the Securities Exchange Act of 1934, as amended (the "Exchange Act"), since the
end of the Registrant's 1996 fiscal year; and (3) the description of the Common
Stock contained in the Registrant's registration statement on Form 8-A filed
with the SEC under Section 12(g) of the Exchange Act, including any amendment or
report filed for the purpose of updating such description.

    In addition, all documents subsequently filed by the Registrant pursuant to
Sections 13(a), 13(c), 14 and 15(d) of the Exchange Act prior to the filing of a
post-effective amendment which indicate that all securities offered hereby have
been sold or which deregister all of such securities then remaining unsold,
shall be deemed to be incorporated by reference into this Registration Statement
and to be a part hereof from the date of filing of such documents.


Item 4.  Description of Securities

    Not applicable.


Item 5.  Interests of Named Experts or Counsel

    Not applicable.


Item 6.  Indemnification of Directors and Officers

    Section 145 of the Delaware General Corporation Law empowers a Delaware
corporation to indemnify its officers and directors and certain other persons to
the extent and under the circumstances set forth therein.

    The Restated Certificate of Incorporation and the Amended and Restated
By-Laws of the Company, copies of which are filed herein as Exhibits 4.1 and
4.2, provide for advancement of expenses and indemnification of officers and
directors of the Registrant and certain other persons against liabilities and
expenses incurred by any of them in certain stated proceedings and under certain
stated conditions to the fullest extent permissible under Delaware law.

    The Company intends to maintain insurance for the benefit of its directors
and officers insuring such persons against certain liabilities, including
liabilities under the securities laws.


Item 7.  Exemption from Registration Claimed

    Not applicable.

<PAGE>

Item 8.  Exhibits

    The following exhibits are filed as part of this Registration Statement:

    4.1  Restated Certificate of Incorporation of the Registrant.  Incorporated
         by reference to Exhibit 3.3 to the Registrant's Registration Statement
         Form S-1 (File No. 333-6795).

    4.2  Amended and Restated By-Laws of the Registrant.  Incorporated by
         reference to Exhibit 3.4 to the Registrant's Registration Statement on
         Form S-1 (File No. 333-6795).

    5    Opinion and Consent of Bingham, Dana & Gould LLP with respect to the
         legality of the shares being registered.

    23.1 Consent of Bingham, Dana & Gould LLP (included in Exhibit 5).

    23.2 Consent of Coopers & Lybrand L.L.P.

    24   Power of Attorney (included in signature page to Registration
         Statement).

Item 9.  Undertakings

    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 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;

(2) That, for the purpose of determining any liability under the Securities Act
    of 1933, as amended (the "Securities Act"), each such post-effective
    amendment 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;

(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;

(4) That, for purposes of determining any liability under the Securities Act,
    each filing of the Registrant's annual report pursuant to Section 13(a) or
    15(d) of the Exchange Act (and, where applicable, each filing of an
    employee benefit plan's annual report pursuant to Section 15(d) of the
    Exchange Act) that is incorporated by reference in the 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; and

(5) Insofar as indemnification for liabilities arising under the Securities Act
    may be permitted to directors, officers and controlling persons of the
    Registrant pursuant to the foregoing provisions, or otherwise, the
    Registrant has been advised that in the opinion of the SEC such
    indemnification is against public policy as expressed in the Securities 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 Securities Act and will be governed by
    the final adjudication of such issue. 

                                       2

<PAGE>

                                      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 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 Cambridge, Commonwealth of Massachusetts, on this 
23rd day of April, 1997.

          CUBIST PHARMACEUTICALS, INC.
    
    
          By: /s/ Scott M. Rocklage, Ph.D.
             -------------------------------------------
             President and Chief Executive Officer

                                  POWER OF ATTORNEY
                                           
    Each person whose signature appears below hereby appoints Scott M. Rocklage
and Thomas A. Shea and each of them severally, acting alone and without the
other, his/her true and lawful attorney-in-fact with the authority to execute in
the name of each such person, and to file with the Securities and Exchange
Commission, together with any exhibits thereto and other documents therewith,
any and all amendments (including without limitation post-effective amendments)
to this Registration Statement on Form S-8 necessary or advisable to enable the
Registrant to comply with the Securities Act of 1933, as amended, and any rules,
regulations, and requirements of the Securities and Exchange Commission in
respect thereof, which amendments may make such other changes in the
Registration Statement as the aforesaid attorney-in-fact executing the same
deems appropriate.

    Pursuant to the requirements of the Securities Act of 1933, this
Registration Statement has been signed by the following persons in the
capacities and on the date indicated.

    Signature                          Title               Date

    /s/  Scott M. Rocklage   President, Chief Executive    April 22, 1997
         -----------------      Officer and Director
         Scott M. Rocklage  (Principal Executive Officer) 



    /s/ Thomas A. Shea       Treasurer                     April 22, 1997
    ------------------      (Principal Financial
        Thomas A. Shea       and Accounting Officer)  


    /s/ John K. Clarke       Chairman of the Board         April 22, 1997
    -----------------        of Directors
        John K. Clarke


    /s/ Barry Bloom          Director                      April 22, 1997
    -----------------
        Barry Bloom


    /s/ George Conrades      Director                      April 22, 1997
    -------------------
     George Conrades

                                       3

<PAGE>

    /s/ Ellen M. Feeney      Director                      April 22, 1997
    -------------------
        Ellen M. Feeney    


                             Director                      April 22, 1997
    -----------------------
     Terrance G. McGuire     



    /s/ Julius Rebek, Jr.    Director                      April 22, 1997
    -----------------------
    Julius Rebek, Jr.   


                             Director                      April 22, 1997
    -----------------------
     Paul R. Schimmel   

                                       4

<PAGE>

                                  INDEX TO EXHIBITS


Exhibit                                               Sequential
Number                  Description                   Page No.

4.1      Restated Certificate of Incorporation of
         the Registrant.  Incorporated by reference 
         to Exhibit 3.3 to the Registrant's 
         Registration Statement Form S-1 
         (File No. 333-6795).                              --
    
4.2      Amended and Restated By-Laws of the 
         Registrant.  Incorporated by reference 
         to Exhibit 3.4 to the Registrant's 
         Registration Statement on Form S-1 (File
         No. 333-6795).                                    --
    
5        Opinion and Consent of Bingham, Dana & 
         Gould LLP with respect to the legality of 
         the shares being registered.                       7
    
    
23.1     Consent of Bingham, Dana & Gould LLP 
         (included in Exhibit 5).                           8
    
    
23.2     Consent of Coopers & Lybrand L.L.P.                9
    
    
24       Power of Attorney (included in signature 
         page to Registration Statement).                   4

                                       5
[{"type": "S-8", "sequence": "1", "description": "FORM S-8", "secsgml_size_bytes": 15179}]
{"company-data": {"conformed-name": "CUBIST PHARMACEUTICALS INC", "cik": "0000912183", "assigned-sic": "2834", "irs-number": "223192085", "state-of-incorporation": "DE", "fiscal-year-end": "1231"}, "filing-values": {"form-type": "S-8", "act": "33", "file-number": "333-25707", "film-number": "97586026"}, "business-address": {"street1": "24 EMILY ST", "city": "CAMBRIDGE", "state": "MA", "zip": "02139", "phone": "6075761999"}, "mail-address": {"street1": "24 EMILY ST", "city": "CAMBRIDGE", "state": "MA", "zip": "02139"}}
As filed with the Securities and Exchange Commission on April 23, 1997
                                                      File No. 333-________

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

                          SECURITIES AND EXCHANGE COMMISSION
                                Washington, D.C. 20549
                                                      
                                       FORM S-8
                            REGISTRATION STATEMENT UNDER 
                              THE SECURITIES ACT OF 1933

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

                             CUBIST PHARMACEUTICALS, INC.
                (Exact Name of Registrant as Specified in its Charter)

                 DELAWARE                            22-3192085
         (State or Other Jurisdiction of          (I.R.S. Employer 
         Incorporation or Organization)           Identification No.)

                       24 Emily Street, Cambridge, MA 02139
                 (Address of Principal Executive Offices) (Zip Code)

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

                             CUBIST PHARMACEUTICALS, INC.
                     AMENDED AND RESTATED 1993 STOCK OPTION PLAN
                               (Full Title of the Plan)

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

                               Scott M. Rocklage, Ph.D.
                        President and Chief Executive Officer
                             Cubist Pharmaceuticals, Inc.
                                   24 Emily Street
                            Cambridge, Massachusetts 02139
                       (Name and address of Agent for Service)
                                           
                                    (617) 576-1999
             Telephone Number, Including Area Code, of Agent for Service
                                ----------------------
                                      Copies to:

                               Justin P. Morreale, Esq.
                                 Julio E. Vega, Esq.
                              Bingham, Dana & Gould  LLP
                                  150 Federal Street
                                Boston, MA 02110-1726
                                    (617) 951-8000

                           CALCULATION OF REGISTRATION FEE
                                           

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

Title Of Each       Amount        Proposed        Proposed         Amount Of
Class Of            To Be         Maximum          Maximum        Registration
Securities         Registered     Offering        Aggregate             Fee
To Be Registered                  Price          Offering 
                                  Per Share      Price (1)
------------------------------------------------------------------------------
Common Stock, 
$.001 par value    1,500,000         N/A        $8,417,652.91        2,550.80

------------------------------------------------------------------------------
------------------------------------------------------------------------------
(1) The proposed maximum offering price has been estimated pursuant to 
    Rule 457(h) solely for the purpose of calculating the registration fee. 
    It is not known how many shares will be purchased under the Plan or at 
    what price such shares will be purchased. The estimate of the proposed 
    maximum aggregate offering price has been calculated based on (i) the 
    offering of 703,801 shares, being the portion of the shares of Common 
    Stock registered hereby subject to outstanding options under the Plan, at 
    a weighted average exercise price of $2.91 per share, and (ii) the 
    offering of 796,199 shares, being the aggregate number of shares of 
    Common Stock available for issuance upon exercise of stock options to be 
    granted under the Plan, at an exercise price of $8.00 per share, which is 
    the average of the high and low prices of the Registrant's Common Stock 
    as listed on the National Association of Securities Dealers Automated 
    Quotation ("Nasdaq") National Market System on April 21, 1996.
PART II
                                           
                  INFORMATION REQUIRED IN THE REGISTRATION STATEMENT
                                           

Item 3.  Incorporation of Documents by Reference.

    The following documents filed by Cubist Pharmaceuticals, Inc. (the
"Registrant") with the Securities and Exchange Commission (the "SEC") are hereby
incorporated by reference in this Registration Statement:  (1) the Registrant's
Annual Report on Form 10-K for the fiscal year ended December 31, 1996; (2) all
reports previously filed by the Registrant pursuant to Section 13(a) or 15(d) of
the Securities Exchange Act of 1934, as amended (the "Exchange Act"), since the
end of the Registrant's 1996 fiscal year; and (3) the description of the Common
Stock contained in the Registrant's registration statement on Form 8-A filed
with the SEC under Section 12(g) of the Exchange Act, including any amendment or
report filed for the purpose of updating such description.

    In addition, all documents subsequently filed by the Registrant pursuant to
Sections 13(a), 13(c), 14 and 15(d) of the Exchange Act prior to the filing of a
post-effective amendment which indicate that all securities offered hereby have
been sold or which deregister all of such securities then remaining unsold,
shall be deemed to be incorporated by reference into this Registration Statement
and to be a part hereof from the date of filing of such documents.

Item 4.  Description of Securities

    Not applicable.

Item 5.  Interests of Named Experts or Counsel

    Not applicable.

Item 6.  Indemnification of Directors and Officers

    Section 145 of the Delaware General Corporation Law empowers a Delaware
corporation to indemnify its officers and directors and certain other persons to
the extent and under the circumstances set forth therein.

    The Restated Certificate of Incorporation and the Amended and Restated
By-Laws of the Company, copies of which are filed herein as Exhibits 4.1 and
4.2, provide for advancement of expenses and indemnification of officers and
directors of the Registrant and certain other persons against liabilities and
expenses incurred by any of them in certain stated proceedings and under certain
stated conditions to the fullest extent permissible under Delaware law.

    The Company intends to maintain insurance for the benefit of its directors
and officers insuring such persons against certain liabilities, including
liabilities under the securities laws.

Item 7.  Exemption from Registration Claimed

    Not applicable.
Item 8.  Exhibits

    The following exhibits are filed as part of this Registration Statement:

    4.1  Restated Certificate of Incorporation of the Registrant.  Incorporated
         by reference to Exhibit 3.3 to the Registrant's Registration Statement
         Form S-1 (File No. 333-6795).

    4.2  Amended and Restated By-Laws of the Registrant.  Incorporated by
         reference to Exhibit 3.4 to the Registrant's Registration Statement on
         Form S-1 (File No. 333-6795).

    5    Opinion and Consent of Bingham, Dana & Gould LLP with respect to the
         legality of the shares being registered.

    23.1 Consent of Bingham, Dana & Gould LLP (included in Exhibit 5).

    23.2 Consent of Coopers & Lybrand L.L.P.

    24   Power of Attorney (included in signature page to Registration
         Statement).

Item 9.  Undertakings

    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 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;

(2) That, for the purpose of determining any liability under the Securities Act
    of 1933, as amended (the "Securities Act"), each such post-effective
    amendment 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;

(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;

(4) That, for purposes of determining any liability under the Securities Act,
    each filing of the Registrant's annual report pursuant to Section 13(a) or
    15(d) of the Exchange Act (and, where applicable, each filing of an
    employee benefit plan's annual report pursuant to Section 15(d) of the
    Exchange Act) that is incorporated by reference in the 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; and

(5) Insofar as indemnification for liabilities arising under the Securities Act
    may be permitted to directors, officers and controlling persons of the
    Registrant pursuant to the foregoing provisions, or otherwise, the
    Registrant has been advised that in the opinion of the SEC such
    indemnification is against public policy as expressed in the Securities 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 Securities Act and will be governed by
    the final adjudication of such issue. 

                                       2
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 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 Cambridge, Commonwealth of Massachusetts, on this 
23rd day of April, 1997.

          CUBIST PHARMACEUTICALS, INC.
    
    
          By: /s/ Scott M. Rocklage, Ph.D.
             -------------------------------------------
             President and Chief Executive Officer

                                  POWER OF ATTORNEY
                                           
    Each person whose signature appears below hereby appoints Scott M. Rocklage
and Thomas A. Shea and each of them severally, acting alone and without the
other, his/her true and lawful attorney-in-fact with the authority to execute in
the name of each such person, and to file with the Securities and Exchange
Commission, together with any exhibits thereto and other documents therewith,
any and all amendments (including without limitation post-effective amendments)
to this Registration Statement on Form S-8 necessary or advisable to enable the
Registrant to comply with the Securities Act of 1933, as amended, and any rules,
regulations, and requirements of the Securities and Exchange Commission in
respect thereof, which amendments may make such other changes in the
Registration Statement as the aforesaid attorney-in-fact executing the same
deems appropriate.

    Pursuant to the requirements of the Securities Act of 1933, this
Registration Statement has been signed by the following persons in the
capacities and on the date indicated.

    Signature                          Title               Date

    /s/  Scott M. Rocklage   President, Chief Executive    April 22, 1997
         -----------------      Officer and Director
         Scott M. Rocklage  (Principal Executive Officer) 

    /s/ Thomas A. Shea       Treasurer                     April 22, 1997
    ------------------      (Principal Financial
        Thomas A. Shea       and Accounting Officer)  

    /s/ John K. Clarke       Chairman of the Board         April 22, 1997
    -----------------        of Directors
        John K. Clarke

    /s/ Barry Bloom          Director                      April 22, 1997
    -----------------
        Barry Bloom

    /s/ George Conrades      Director                      April 22, 1997
    -------------------
     George Conrades

                                       3
/s/ Ellen M. Feeney      Director                      April 22, 1997
    -------------------
        Ellen M. Feeney    

                             Director                      April 22, 1997
    -----------------------
     Terrance G. McGuire     

    /s/ Julius Rebek, Jr.    Director                      April 22, 1997
    -----------------------
    Julius Rebek, Jr.   

                             Director                      April 22, 1997
    -----------------------
     Paul R. Schimmel   

                                       4
INDEX TO EXHIBITS

Exhibit                                               Sequential
Number                  Description                   Page No.

4.1      Restated Certificate of Incorporation of
         the Registrant.  Incorporated by reference 
         to Exhibit 3.3 to the Registrant's 
         Registration Statement Form S-1 
         (File No. 333-6795).                              --
    
4.2      Amended and Restated By-Laws of the 
         Registrant.  Incorporated by reference 
         to Exhibit 3.4 to the Registrant's 
         Registration Statement on Form S-1 (File
         No. 333-6795).                                    --
    
5        Opinion and Consent of Bingham, Dana & 
         Gould LLP with respect to the legality of 
         the shares being registered.                       7
    
    
23.1     Consent of Bingham, Dana & Gould LLP 
         (included in Exhibit 5).                           8
    
    
23.2     Consent of Coopers & Lybrand L.L.P.                9
    
    
24       Power of Attorney (included in signature 
         page to Registration Statement).                   4

                                       5