This chapter reviews the biology of adenoviruses, clinical trials of oncolytic viral gene therapy in ovarian cancer and recent developments that may give cause for cautious optimism. There are 49 serotypes of human adenoviruses, divided into six groups. There have only been a small number of clinical trials of gene therapy in ovarian cancer. Mutations in p53 are almost universal in high-grade serous ovarian cancer, there were early attempts to re-introduce wild-type p53 gene expression using a non-replicating adenovirus. Following primary debulking surgery, women whose tumours had demonstrable p53 mutations were randomised to conventional platinum and paclitaxel chemotherapy with or without IP SCH58500. Most importantly, there remain many questions about the biology of adenoviruses that are unanswered-many of these relate to the role of host cell factors in determining cell fate following infection and the potential role of immune responses in cell death in whole organisms.