The renin-angiotensin-aldosterone system (RAAS) plays an integral role in blood pressure regulation and has long been a target of pharmacologic approaches to controlling blood pressure. Traditionally, clinical interventions involving the RAAS have focused mainly on inhibiting the action of angiotensin II with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, and limited attention has been devoted to direct inhibition of the action of aldosterone. Recent advances in understanding the role of aldosterone in cardiovascular injury have elevated the importance of direct inhibition of the action of this hormone in the long-term control of blood pressure and have led to the development of the selective aldosterone blocker eplerenone. This article reviews the role of the RAAS in the development of hypertension and discusses the rationale for the use of eplerenone with other medications affecting the RAAS to control blood pressure.