The purpose of the present article was to review the current evidence on the use of angiotensin-converting enzyme (ACE) inhibitors in acute myocardial infarction (MI). This article is based on published information as well as on our personal experience derived from an extensive analysis of the SMILE study. All the randomized trials have been included irrespective of the primary endpoint, and the results are presented in terms of either hemodynamic or clinical benefit. Short- and long-term treatment with ACE inhibitors in patients with acute MI results in a significant reduction in mortality, which is more evident in high risk patients (i.e., patients with left ventricular dysfunction, congestive heart failure on admission, or anterior myocardial infarction). Development and progression of congestive heart failure after myocardial infarction was significantly reduced by ACE inhibition, which also reduced the rate of reinfarction, the need for revascularization procedures, as well as the occurrence of ventricular arrhythmias, probably through a mechanism involving some drug-dependent effects. In conclusion, the available data strongly support a wide benefit associated with the use of ACE inhibitors in patients with high-risk acute MI.