The early detection of ovarian cancer represents a clinical objective with an enormous potential for a meaningful improvement in our ability to treat and cure afflicted patients. The magnitude of this potential is matched by the challenges associated with attaining it. In addition to the well noted aspects of ovarian cancer which have thus far precluded the development a effective screening strategies, recent work regarding the differential pathogenesis and origins of the various histological subtypes of epithelial ovarian cancer have further revealed the challenges ahead. These findings are reviewed here with a particular focus on reports describing the early development of high-grade serous carcinomas, the most prevalent and aggressive disease subtype. The unique set of difficulties associated with the early detection of these tumors is discussed in depth. An update on findings stemming from several large randomized screening trials is provided. While the current state of ovarian cancer screening remains characterized by unmet needs, the ongoing evaluation of those needs is providing a strong basis for future advancement. This advancement will rely upon the refined application of currently available diagnostic tools based on lessons well learned.