The endothelium modulates vascular tone by the release of vasodilator and vasoconstrictor substances, among them nitric oxide (NO) and endothelin (ET). Abnormalities in NO generation have been demonstrated in various cardiac pathophysiological states, specifically atherosclerotic vascular disease, congestive heart failure, and essential and pulmonary hypertension, Moreover, increases in plasma ET has been reported as well in these disease states, When these observations are taken together, these states may be characterized by an attenuated release of NO, whereas the release of ET is augmented, An imbalance between NO and ET may contribute to the alteration in vascular tone characteristic of cardiovascular disease, The following review summarizes the present knowledge of the role of NO and ET in such disease processes with a major focus on coronary endothelial dysfunction.