The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are the second most prescribed therapeutic drug class in the United States after analgesics. Although these agents are used predominantly to reduce cholesterol concentrations in patients with hyperlipidemia, numerous studies have investigated the pleiotropic effects of statins and their potential in the prevention and/or treatment of other disease states, including cancer. Many theories have been proposed as to how statins may affect the risk or development of malignancies, prompting a clinical review of the literature. Studies have revealed statins to be associated with both increased and decreased cancer risk. Most of the published studies have been observational and retrospective in nature, and most prospective trials evaluated cancer as a secondary end point or adverse event, making it difficult to determine causality. Although most of the available evidence suggests a possible beneficial effect of statins on cancer, further study is needed with better designed trials and/or increased efforts in evaluating cancer as secondary end points in all statin trials until definite conclusions regarding statin effects on cancer risk and occurrence can be made.