The development of heart failure and/or left ventricular systolic dysfunction following acute myocardial infarction remains prevalent despite improvements in the diagnosis and management over the past decades. Although transient in some cases, the majority of these patients continue to carry a substantially higher mortality risk. New data on the benefits of eplerenone and carvedilol from large clinical trials have added to the complexity of polypharmacy in this patient subgroup, although aggressive medical strategies to prevent or reverse infarct-related left ventricular remodeling remains the most effective method to save lives and prevent disabilities.