The rationale for ketanserin therapy in hypertension is reviewed against the background of known physiological and pathophysiological effects of serotonin. The usefulness of the serotonin (5-HT2) antagonist ketanserin in the treatment of hypertension is evaluated with respect to its known antihypertensive property as well as in relation to its effect on hypertension-induced cardiovascular changes, platelet hyperreactivity, and atheroma formation. Based on ketanserin's documented antihypertensive effect and also on its potentially positive effect on cardiovascular mortality via other mechanisms, it would appear that ketanserin could offer a highly rational approach to the treatment of hypertension and its risks in the future.