Myocardial perfusion abnormalities occur in the absence of epicardial coronary artery disease in patients with a wide spectrum of cardiovascular disorders including microvascular angina, hypertension and left ventricular hypertrophy, coronary atherosclerosis, hypercholesterolemia, and non-ischemic left ventricular dysfunction. These patients have limited coronary microvascular dilator reserve which occasionally is associated with evidence of myocardial ischemia. Primary microvascular hyperconstriction (spasm) is also proposed to cause myocardial ischemia in a subset of patients with rest angina. There is ample evidence suggesting that endothelial dysfunction contributes to microvascular dysfunction, but the precise mechanism of endothelial dysfunction is not known. Nitric oxide is one of the key molecules which control microvascular tone and therefore coronary blood flow, and its decreased availability appears to be involved under certain conditions. This hypothesis has attracted considerable interest as a new therapeutic strategy for these patients having coronary microvascular derangements caused by divergent cardiovascular diseases.