Our limited understanding of the natural biology of ovarian cancer, along with its low prevalence in the general population make early detection especially challenging. To be successful at the population level, an ovarian cancer screening test must prove its beneficial effect on ovarian cancer-specific mortality while achieving near-perfect specificity in order to minimize the harms resulting from false-positive results. No current screening tests for ovarian cancer fulfill these expectations. We review the current status and the challenges of ovarian cancer screening in the context of evidence-based principles that define a valuable cancer screening program.