The role of the renin-angiotensin system as a regulator of blood pressure, body fluids, electrolytes, and neurohormonal activation has been established for more than two decades. The dramatic benefits of angiotensin-converting enzyme (ACE) inhibition on overall mortality, progression to heart failure, and major cardiovascular events were first demonstrated in patients with congestive heart failure (CHF) or left ventricular dysfunction. ACE inhibitors should be prescribed for all patients with symptomatic CHF and for all asymptomatic patients with a left ventricular ejection fraction less than 35% to 40%, unless contraindicated or not tolerated, and therapy should be continued indefinitely. Data have shown that ACE inhibition improves oxidative stress, endothelial and ventricular function, and reduces ventricular remodeling as well as progression of carotid intimal and medial thickening. Current evidence suggests that ACE inhibitors should be prescribed as early as possible for all patients with acute myocardial infarction, unless contraindicated or not tolerated, and that they should be continued for at least 6 weeks; moreover, because these patients automatically qualify as high-risk individuals, indefinite therapy should be considered. Likewise, individuals at increased risk for major cardiovascular events (diabetic patients with additional risk factors and patients with known vascular disease) should be prescribed ACE inhibitors, unless contraindicated or not tolerated, and therapy should be continued indefinitely. There is not sufficient evidence at present to recommend the use of ACE inhibitors after coronary revascularization for the specific goal of preventing restenosis or graft disease, in the absence of decreased ejection fraction, CHF, or a new myocardial infarction.