In this article, we review the evidence supporting the use of eplerenone for improving cardiovascular prognosis. Activation of the renin-angiotensin-aldosterone system plays a major role in the pathogenesis of heart disease, and blockage of this system has been shown to improve prognosis in several cardiovascular conditions. The 2 marketed aldosterone antagonists, spironolactone and eplerenone, improve prognosis in patients with left ventricular (LV) dysfunction and are effective antihypertensive medications. In addition, a potential role for aldosterone antagonists in the treatment of patients with heart failure and preserved LV function has been suggested and is currently being evaluated in clinical trials. In patients with myocardial infarction having LV dysfunction and evidence of heart failure, eplerenone improves cardiovascular outcomes and attenuates myocardial remodeling. In addition, eplerenone is effective for the treatment of hypertension, where it regresses both LV hypertrophy and proteinuria (2 powerful markers of increased cardiovascular risk). In contrast to spironolactone, eplerenone essentially lacks the sexual side effects that sometimes limit the use of spironolactone. Hyperkalemia is the main potential side effect of eplerenone, especially when used in combination with other medications that can cause hyperkalemia. Adequate patient selection and monitoring are therefore of utmost importance when using this medication. In conclusion, eplerenone is a medication that offers the cardiovascular therapeutic and prognostic benefits of aldosterone antagonism but with fewer side effects compared to spironolactone.