The search for an effective screening test for the early detection of ovarian cancer has been intensive. Transvaginal ultrasound and the serum biomarker cancer antigen 125 (CA125) have been used clinically for decades in high-risk populations despite the lack of evidence demonstrating efficacy. More recently, new technologies have identified novel biomarker panels that attempt to improve on the performance of currently available modalities. Some of these tests report superior performance characteristics (sensitivity, specificity, positive predictive value) when compared with CA125 testing alone. Based on early encouraging studies, two commercial ovarian cancer screening products were recently marketed to the public and medical community. They were both withdrawn after concerns were raised by the US FDA and the scientific community regarding their validation and efficacy. There is no clear and established pipeline for the development and approval of these types of tests, and the FDA is working to fill in a large regulatory gap. In order to minimize the potential for public harm, an ovarian cancer screening test will need to be appropriately tested before being made available to the general population. In this review, we discuss the current state of biomarker development for the early detection of ovarian cancer and explore the continuing challenges to realizing this goal.