Statins are HMG-CoA reductase inhibitors with important cholesterol-lowering properties. The introduction of these agents in clinical medicine has had a major impact and has changed the natural history of coronary artery disease in humans. Beyond their cholesterol-lowering properties, statins exhibit important anti-inflammatory and antitumor activities. Extensive studies over the last few years have demonstrated that statins generate pro-apoptotic, growth inhibitory, and pro-differentiation responses on neoplastic cells of diverse origin. In addition, several cellular pathways activated by statins have been identified and key mechanisms involved in the generation of their antitumor effects have been characterized. Because of such in vitro effects, extensive efforts are underway to establish their utility in cancer prevention and their potential use in the treatment of certain malignancies, in combination with other agents. This review summarizes the documented effects of statins on different tumor cell types and discusses the cellular mechanisms of action of statins in malignant cells. The clinical-translational implications of the ongoing research efforts are also discussed.