Ovarian cancer (OC) is the fourth leading cause of cancer deaths among women in the United States, despite its relatively low incidence of 50 per 100,000. Even though advances in therapy have been made, the OC fatality-to-case ratio remains exceedingly high, due to the lack of accurate tools to diagnose early-stage disease when cure is still possible. The most studied marker for OC, CA125, is only expressed by 50-60% of patients with early stage disease. Large efforts have been deployed to identify novel serum markers, yet no single marker has emerged as a serious competitor for CA125. Various groups are investing in combination approaches to increase the diagnostic value of existing markers, but many markers may still lie in under-explored areas of ovarian cancer biology, such as tumor vasculature environment and post-translational modifications (glycomics).