The endothelium integrates and modulates critical functions of the arterial wall. As well as regulating vasomotion, it controls inflammation, coagulation, and thrombosis. Many of these actions are mediated through the release of nitric oxide. Endothelial dysfunction is associated with atherosclerosis and its risk factors. It is independently correlated to adverse cardiovascular events, including myocardial infarction, coronary death, and the need for revascularization. 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) protect against cardiovascular death, myocardial ischemia, myocardial infarction, and stroke. Although cholesterol reduction accounts for some of these benefits, others appear to be independent of cholesterol lowering. The endothelium mediates many of these "lipid-dependent" and "lipid-independent" actions of statins. This chapter reviews the effects of statins on endothelial dysfunction. To do so, a brief outline of the biology of the endothelium is a prerequisite. This will be followed by a summary of the advances in vascular research on cholesterol-dependent and cholesterol-independent effects of statins, with a focus on the endothelium. Ultimately, clinical relevance of observations derived from basic biology will be discussed.