Preclinical gene-therapy studies in the past 15 years have repeatedly raised hopes that we were about to enter a brave new era. However, many clinical trials have disappointed. For tumor types with poor response rates to first-line conventional cytotoxic chemotherapy and/or high rates of chemorefractory disease, there remain very few treatment options. In this article we review gene therapy within the context of ovarian cancer. We examine why clinical data have been discouraging and discuss how the lessons learned from earlier trials are being applied to current research.