The vascular endothelium plays an essential role in regulating blood flow and other functions of the coronary arteries. Under normal conditions, the endothelium releases a number of factors that regulate arterial vasomotion. One of these factors, endothelial-derived relaxing factor (EDRF), is a vasorelaxant that is identical to, or closely related to, nitric oxide (NO). Endothelial function may be compromised in coronary artery disease (CAD) or in the presence of risk factors for CAD. In this setting, EDRF-NO activity is inhibited, which may lead to vasoconstriction, platelet aggregation, vasospasm, and thrombosis. The relation between endothelial function, arterial vasomotion, and myocardial ischemia is discussed, with particular emphasis on the role of EDRF-NO, and the therapeutic interventions that may be useful in treating the clinical consequences of endothelial dysfunction.