Since its discovery in 1988, endothelin (ET) has been widely implicated in the pathophysiology of cardiovascular disease. ET antagonists have favourable effects in experimental models of these conditions and have proved useful in elucidating the role of the ET system. Orally acting ET antagonists appear very promising in clinical trials, particularly in patients with chronic heart failure and hypertension, but more information on the roles of the ET receptor subtypes in health and disease is required so that an informed choice can be made between the use of endothelin-A (ET-A) receptor-selective and nonselective receptor antagonists.