Ovarian cancer (OVCA) has the highest mortality of all gynecologic cancers. The poor survival rate is due to the lack of diagnostic screening tests and high incidence of recurrence in OVCA patients resistant to chemotherapy that leads to a more aggressive form of the disease. Therefore, a search for biomarkers holds great promise not only for early detection of OVCA at presymptomatic stage and for monitoring the course of the disease during the first-line chemotherapy treatment but also for identifying those women whose disease is likely to recur. Research efforts have sought to unravel the complexity of the tumor specific proteome by profiling immune responses generated against tumor associated antigens (TAAs) using multianalyte-based analytical discovery platforms readily adaptable to clinical diagnostic screening tests. The occurrence of tumor-specific autoantibodies directed to respective TAAs can be observed before the development of clinical symptoms. Evaluation of the level of tumor autoantibodies during the time of tumor debulking followed by first-line chemotherapy for the prediction of early recurrence as well as their correlation with other clinical parameters to evaluate their prognostic value has been conducted in various clinical studies. The anti-tumor immune response against OVCA is the ultimate key to the development of multiple immune-based therapeutic strategies that have been proposed and tested in different clinical trials that may have beneficial impact on the disease outcome in OVCA patients.