Ovarian cancer is associated with an overall mortality of 75%, but can be cured in up to 90% of cases if diagnosed while still limited to the ovaries. Given the low prevalence of ovarian cancer in the general population, an effective screening strategy must not only have a high sensitivity for early-stage disease (>75%), but must also have a very high specificity (99.6%) to prompt no more than ten operations for each case of ovarian cancer diagnosed (positive predictive value [PPV] of 10%). Attempts to develop an effective screening strategy for ovarian cancer have utilized ultrasonography and serum tumor markers. Transvaginal sonography (TVS) and the serum marker CA125 have received the most attention to date. Used individually on a single occasion, neither of these approaches provides an adequate PPV and the cost of annual TVS is significant. Recent clinical trials have focused on serial monitoring of CA125 and the sequential use of a rising CA125 to prompt TVS in a limited number of women screened. Sequential monitoring of CA125 has significantly improved specificity of the assay in women over 50 years of age. The limited sensitivity of CA125 has, however, prompted a search for multiple serum markers that, in combination, would detect more than 90% of early-stage disease. Recent developments in genomic and proteomic research have identified a number of candidate biomarkers. Platforms have been developed that can assay more than 50 analytes in a few hundred microliters of serum. Panels of biomarkers have been discovered with high sensitivity and specificity for early-stage disease, but these require prospective validation. Several biomarkers have also been detected in urine, raising the possibility of a less expensive, more convenient screening test. Imaging techniques have been improved and mathematical methods developed that, in aggregate, promise to provide an effective screening strategy for ovarian cancer. In this review, we will assess the current status and describe future directions in ovarian cancer screening.