This paper reports the rationale for the cardiovascular protective effects of angiotensin-converting enzyme (ACE) inhibitors and reviews the overall results of recent randomized clinical trials. ACE-inhibitors prevent degradation of bradykinin, exert anti-ischemic action, inhibit thrombosis and platelet aggregation, are antiatherogenic, improve endothelial function and vessel remodeling, and have anti-inflammatory properties. Previous trials have shown that ACE-inhibitors reduce cardiovascular events in patients with heart failure or ventricular dysfunction. These findings have recently been extended to patients with lower risk profile, no evidence of heart failure and in secondary prevention using lipophilic ACE-inhibitors with high affinity for tissue ACE, i.e. those most likely to have high antiatherosclerotic efficacy. The central role of long-acting lipophilic ACE-inhibitors for cardiovascular protection has been clearly established and they should now be considered as a routine treatment for secondary prevention in the same way as aspirin, beta-blockers and statins.