Pharmacological antagonism of the endothelin system presents a novel target for the treatment of a range of cardiovascular diseases. The antagonists developed so far differ in their endothelin receptor subtype specificity. Indeed, at present there is no consensus opinion as to what level of receptor selectivity defines a particular antagonist as 'selective' or 'mixed'. Antagonists that are highly selective for the endothelin A receptor (ETA) receptor subtype have a number of hypothetical advantages over non-selective antagonists. This theory is based on the analysis of the function of the endothelin B (ETB) receptor. Current evidence suggests that activation of the ETB receptor results in vasodilatation, diuresis and natriuresis, each of which are properties that might be advantageous to maintain in conditions such as cardiac failure and hypertension. However, definitive evidence to suggest a therapeutic advantage of selective ETA receptor antagonists requires long-term, head-to-head studies to be performed.