Effective antihypertensive therapy has made a major contribution to the reductions in the morbidity and mortality of cardiovascular disease that have been achieved since the 1960s. However, blood-pressure control with conventional drugs has not succeeded in reducing cardiovascular disease risks to levels seen in normotensive persons. Drugs that inhibit or antagonize components of the renin-angiotensin-aldosterone system are addressing this deficiency by targeting both blood pressure and related structural and functional abnormalities of the heart and blood vessels, thus preventing target-organ damage and related cardiovascular events.