The presence of heart failure or left ventricular systolic dysfunction in the setting of acute myocardial infarction is associated with poor prognosis. Aldosterone is an important downstream mediator of the renin-angiotensin-aldosterone system that promotes myocardial collagen deposition, myocardial fibrosis, apoptosis, ventricular remodeling, and endothelial dysfunction. It may play an important role in the increased morbidity and mortality and the development and progression of heart failure after acute myocardial infarction. Extending the findings from the Randomized Aldactone Evaluation Study (RALES) in patients with chronic heart failure, the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) demonstrated that the selective aldosterone blocker eplerenone offered a significant survival benefit, attenuation of progression of heart failure, and prevention of sudden cardiac death when used in addition to optimal medical therapy. The current evidence-based guidelines now suggest that aldosterone blockade should be an integral component of heart failure therapy to improve outcomes in this high-risk population.