Gene therapy remains a promising therapeutic modality for ovarian cancer. Yet much work remains to be done to see gene therapy realize its full potential in elucidating the complex genetic interactions of delivered genes within target cancer cells and in the development of improved vector systems. Because most neoplasms involve multiple mutations, the targeting of a single mutation is unlikely to achieve total tumor control; gene therapy strategies that target multiple cellular processes or invoke various antitumor approaches need to be investigated. Additionally, current vector systems do not transduce ovarian cancer cells efficiently and are hampered by immune responses that further limit their efficacy. Additionally, limitations in vector specificity lead to transduction of normal cells and subsequent toxicity. Investigators are developing refinements to current gene therapy approaches that would address these limitations and that are soon to be incorporated into clinical trials. It is hoped that these advances will lead to improvements in the therapeutic index for ovarian cancer gene therapy and provide another effective therapeutic tool for this deadly disease.