The term endothelial dysfunction most commonly refers to impairment of endothelium-dependent vasodilation and implies presence of widespread abnormalities in endothelial integrity and homeostasis. This phenomenon, which can be measured by a number of invasive and noninvasive techniques, often marks an early stage in atherosclerosis and can be observed in coronary and peripheral arterial beds. Studies demonstrate that endothelial dysfunction in the coronary resistance or conductance vessels predict both hard (eg, acute ischemic events) and soft (eg, coronary revascularization) outcomes. Other studies demonstrate that endothelial dysfunction of the brachial artery also carries prognostic relevance for risk of coronary events. However, these studies included selected high-risk populations. Data are lacking on the prognostic value of endothelial dysfunction in low-risk populations. Further, the data do not permit the use of improvement in endothelial dysfunction as a surrogate marker for risk reduction. Nevertheless, assessment of endothelial function is a valuable research tool and, with further refinement, promises to be an important aid in applying the science of vascular biology to clinical practice.