Serotonin is a naturally occurring vasoactive substance that has diverse cardiophysiological effects. These effects can be explained by the existence of serotonin receptor subtypes which mediate different biological actions. The vasoconstrictive actions of serotonin are mediated by 5-HT2 serotonergic receptors, and serotonin also amplifies the release and activities of other vasoconstrictors, such as angiotensin and norepinephrine. Abnormalities in the serotonergic system may play an important role in the pathophysiology of multiple cardiovascular disease states such as systemic hypertension, primary pulmonary hypertension and peripheral vascular disease. Selective 5-HT2 serotonergic receptor blockers have been developed which appear to be potent vasodilators with therapeutic potential in various cardiovascular disease states. The largest clinical experience has been collected with ketanserin, and other agents in this class are being investigated. Prolongation of the ECG QT interval with 5-HT2 serotonergic receptor blockers may pose a potential risk with these treatments in some patients.