Despite advances in therapy, advanced ovarian cancer maintains a dismal overall survival of 15-30%. Thus, the need for novel therapeutic modalities exists. Gene therapy represents one such approach and the purpose of this review is to present a logical rationale for the investigation of gene therapy for the treatment of ovarian cancer. The different strategies of gene therapy (molecular chemotherapy (prodrugs), mutation compensation, immunotherapy approaches, altered drug sensitivity, and virotherapy) for cancer treatment are discussed separately with attention to investigations with clinical applicability. Furthermore, the different viral vectors utilized for improvements in targeted therapy are presented. The advancements, discovery, and shortcomings are reviewed which lend itself to future directions. These future directions involve coxsackie-adenovirus receptor (CAR) independent pathways to improve infectivity and specificity to ovarian tumor cells, the potential of utilizing gene therapy as an imaging modality in detecting cancer, and incorporating the recently described technique of RNA interference. Due to the advancements in detection and targeting of ovarian cancer, coupled with the containment to the intraperitoneal cavity, gene therapy remains a promising treatment modality for ovarian cancer.