Ovarian cancer is the most lethal of the gynecological cancers because its etiology is not well understood and majority of ovarian cancers are detected at advanced stage, at which point it is typically incurable. Effective screening protocols and earlier disease detection and diagnosis could result in decreased morbidity for women with ovarian cancer. Cancer antigen 125 (CA-125) is the most frequently used diagnostic biomarker for ovarian cancer; however, it is not overexpressed in the early stage of the disease. Moreover, levels of CA-125 are also elevated in other instances, such as benign ovarian tumors and gynecological inflammation. Investigators are searching for new, specific, and sensitive biomarkers to replace or complement CA-125 in detection of ovarian cancer at an early stage. This review discusses current status and new biomarkers, algorithms for screening, and risk assessment for ovarian cancer.