Although ovarian cancer (OC) is the most lethal of all female malignancies, debate still exists concerning the benefits and harms of the screening programs and their impact on long-term survival and mortality from the disease. The most widely tested screening strategies have focused on transvaginal ultrasound (TVU) and on algorithms that measure serum levels or interval changes of cancer antigen-125 (CA-125) either individually or in combination. Transvaginal ultrasound can identify size and morphology changes of the ovary that may signal a developing malignancy; yet, it is still accused of having a low specificity. There is preliminary evidence that screening can improve survival, but the impact of screening on mortality from OC is still unclear and warrants further validation. In spite of having many published prospective studies, up to-date, none have been able to demonstrate conclusively a reduction in mortality from OC both in the screened general or high-risk population. Data from the US Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial has not shown survival or mortality benefits in the general population. Most prospective trials have reported a decrease in stage at detection (with the exception of the PLCO trial), thereby allowing treatment to be initiated when the disease is most curable. Research is in progress to develop new diagnostic tests and novel biomarkers, which when used in combination can increase the accuracy and outcomes of screening. In this review article, we will discuss the debate provoked on OC screening programs and the impact of using ultrasound on the reduction of OC-related mortality.