Ovarian cancer is the most common gynaecological cancer and the one with the highest mortality. Advances in standard treatments for this disease, such as chemotherapy and combined surgery, have not significantly improved patient survival. Complications of advanced ovarian cancer include the production of large amounts of ascites fluid containing cancer cells. New alternative therapies such as TRAIL, a death receptor ligand which kills tumour cells, are needed. The ability of TRAIL to selectively induce tumour cell death makes it an attractive agent for cancer therapy. The malignant ascites fluid may contain factors that could promote escape of tumour cells against TRAIL-induced cell death. Thus, to implement and optimize therapy of ovarian cancer patients with TRAIL, it is important to understand how ascites fluid may influence TRAIL-induced cell death. Our preliminary data show that malignant ascites fluid protects ovarian cancer cells against TRAIL-induced cell death by activating intracellular pro-survival signalling pathways. Understanding how these pathways are regulated will provide important insights that will help design better TRAIL-based strategies for treatment of ovarian and other cancers.