Endothelial dysfunction is an early and persistent vascular abnormality in the evolution of atherothrombotic disease. Risk factors for atherosclerosis promote an inflammatory oxidative environment in the vasculature that induces pathologic changes in endothelial function, including the support of enhanced smooth muscle tone, thrombosis, and smooth muscle proliferation. This article provides an overview of the molecular basis of endothelial dysfunction and of its diagnosis and treatment.