Statins are inhibitors of the 3-hydroxy-3-methylglutaryl coenzyme A reductase, a ubiquitous enzyme critical for the biosynthesis of cholesterol. Because of their cholesterol-lowering properties, statins are extensively used in medical practice, and large clinical trials have shown that statins effectively reduce cardiovascular related morbidity and mortality. In the past 5 years, an important, new concept suggesting that the cardioprotective effects of statins are not necessarily related to cholesterol-lowering actions has emerged. Indeed, in vivo findings have clearly shown that statins exert anti-inflammatory and immunomodulatory effects and that they modulate vascular remodeling under normocholesterolemic conditions. These pleiotropic properties of statins affect important molecules in vascular biology and help preserve endothelial function in acute and chronic inflammatory states of the cardiovascular system, including coronary and cerebral artery diseases, diabetes, and atherosclerosis. Emerging evidence indicates that the microcirculation is a crucial target for the pleiotropic actions of statins because of its important role in regulating blood flow, leukocyte-endothelium interactions, and vascular remodeling. Accordingly, this review focuses on the role that the microcirculation plays in the vascular protective action of statins.