Angiotensin-converting enzyme (ACE) inhibitors play an important role in protecting various organs in patients with congestive heart failure. The mechanisms of action of ACE inhibitors in congestive heart failure are multiple and may involve important effects on endothelial function in addition to the well known hemodynamic and neurohormonal effects. Skeletal muscle fatigue can play an important role in the pathophysiology of congestive heart failure, and only aggressive treatment with ACE inhibitors and exercise training can improve exercise tolerance and reduce the risk of further deterioration of cardiac function. ACE inhibitors should be introduced with caution in patients with severe heart failure and hypotension to prevent renal dysfunction. Unlike some other ACE inhibitors, perindopril seems to cause no first dose hypotension. It also appears to have a neutral effect on renal function in patients with severe congestive heart failure.