Traditionally, the rennin–angiotensin system (RAS) has been viewed as an endocrine system. Recently, independent tissue RASs have been postulated that are believed to act in a paracrine/autocrine fashion. Elements of the RAS have been shown to exist in many peripheral tissues. Angiotensin-converting enzyme (ACE), a key element of the RAS, is found mainly in the vascular endothelium and therefore represents the main target site for inhibition of the local and circulating RASs. In the heart, angiotensin II exerts a direct positive inotropic and chronotropic effect. More recently, it was also found that angiotensin II may act as a growth factor in several cell types. Angiotensin II is also thought to be partially responsible for structural remodeling in cardiac hypertrophy. The role of ACE inhibitors has been established in the treatment of hypertension and congestive heart failure. Recent multicenter trials revealed a beneficial role of ACE inhibitors in reduction of mortality rates in patients with congestive heart failure and a low ejection fraction. Mechanisms that include reduction of myocardial oxygen demand, improvement of coronary blood flow, induction of capillary proliferation, reduction of blood pressure and ventricular wall tension without reflex tachycardia, and impairment of myocardial contractility are the basis for the beneficial effects of ACE inhibitors. In addition to a reduction of angiotensin II generation, these effects appear to be largely brought about by the inhibition of endogenous kinin degradation. Recent studies suggest that a deletion polymorphism in the gene encoding ACE is a risk factor in myocardial infarction (MI). In the future, ACE genotyping might identify patients in whom ACE-inhibitor treatment is most likely to prevent MI.