Abstract Vascular endothelium plays a pivotal role in the maintenance of vasodilation and the inhibition of platelet aggregation and smooth muscle cell proliferation through the release of nitric oxide and other factors. Extensive data have demonstrated abnormalities in coronary endothelial function in the epicardial coronary arteries in patients with atherosclerosis or risk factors for atherosclerosis. This dysfunction leads to abnormal vasoconstriction and platelet aggregation, which likely play a role in producing ischemia in patients with coronary artery disease. Invasive techniques have been available to assess endothelium-dependent vasodilator responses in the coronary arteries. However, until recently little has been known about endothelial responses in the peripheral vasculature, as methods to assess this have not been readily available. The hypothesis that endothelial dysfunction is a systemic process is explored, and new noninvasive methods of assessing endothelial function are discussed.