Cancer is a disease of a series of genes. Thus, theoretically, brain tumors could be treated by targeting their fundamental molecular defects. Currently, most of the approved clinical protocols for gene therapy involve cancer patients. Several of these protocols are designed to improve the treatment of brain tumors. In this brief report, we analyze the rationale, advantages, and disadvantages of a series of gene therapy approaches against brain tumors that include transfer of tumor suppressor genes and cell-cycle modulators; suicide or prodrug strategies; immunogene therapy; antiangiogenesis; and oncolytic virus therapy. In summary, in this review, we highlight the translational advances in molecular medicine that broaden our battery of therapies for patients with brain tumors.