Angiogenesis is an important process for a variety of physiologic and pathologic conditions. Different angiogenic modulating targets are under extensive investigation both experimentally and clinically. The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are the first-line agents used in hypercholesterolemia. They are also characterized by having other benefits apart from their lipid-lowering effects. Among these pleiotropic effects are the pro- and antiangiogenic properties of statins. The pleiotropic effects of statins and how they modulate new blood vessel formation are discussed in this review. The currently available data from both animal and human studies regarding the effects of statins on angiogenesis in ischemic heart disease, stroke, ocular diseases, and cancer are also reviewed. Statins are safe, orally available agents that may acquire novel therapeutic indications through their angiogenic modulating effects.