Exhibit 5.1

May 18, 2011

ZIOPHARM Oncology, Inc.

1180 Avenue of the Americas, 19th Floor

New York, NY 10036

RE: Statement on Form S-3

Ladies and Gentlemen:

We have acted as counsel for ZIOPHARM Oncology, Inc., a Delaware corporation (the “Company”) in connection with the Company’s filing of a Registration Statement on Form S-3 (the “Registration Statement”) relating to the registration under the Securities Act of 1933, as amended (the “Act”), of the resale by the selling shareholder named therein (the “Selling Shareholders”) of an aggregate of 9,700,087 shares (the “Shares”) of common stock, par value $0.001 per share (the “Common Stock”), of which 6,063,161 are issued and outstanding on the date hereof (the “Original Shares”) and 3,636,926 shares (the “Contingent Shares”) are issuable upon the achievement of a milestone set forth in that certain Stock Purchase Agreement dated January 6, 2011 by and between the registrant and Intrexon Corporation (the “Stock Purchase Agreement”).

In connection with rendering this opinion, we have reviewed the following:  (i) the Company’s certificate of incorporation, as amended to date; (ii) the Company’s bylaws in effect on the date hereof; (iii) the Stock Purchase Agreement (iv) certain resolutions of the Company’s Board of Directors pertaining to the issuance by the Company of the Shares; and (v) such other documents, certificates and records as we deemed necessary or appropriate as a basis for the opinions expressed herein.

Based upon the following and upon the representations and information provided by the Company, we hereby advise you that, in our opinion:

1. The Original Shares have been duly authorized and are validly issued, fully paid and nonassessable; and

2. The Contingent Shares have been duly authorized and the Contingent Shares, when issued in accordance with the terms of the Stock Purchase Agreement upon the satisfaction of conditions set forth therein, will be validly issued, fully paid and nonassessable.

We hereby consent to the filing of this opinion as an exhibit to the Registration Statement and to the reference to our firm under the caption “Validity of Common Stock” included in the Registration Statement and the related Prospectus.

We hereby consent to the filing of this opinion as an exhibit to the Registration Statement in accordance with the requirements of Item 601(b)(5) of Regulation S-K under the Securities Act.  We also consent to the reference to our name under the caption “Validity of Common Stock” in the prospectus filed as part of the Registration Statement.  In giving such consent, we do not hereby admit that we are in the category of persons whose consent is required under Section 7 of the Securities Act or the rules and regulations of the Securities and Exchange Commission.

Very truly yours,

/s/ Maslon Edelman Borman & Brand, LLP