Angiotensin-converting enzyme-inhibitors (ACE inhibitors) were first introduced into clinical practice for the relief of hypertension (HT) more than a quarter of a century ago. Since that time, as the basic pathobiology of cardiovascular (CV) diseases has been increasingly understood, new applications for ACE inhibitors have been developed. Indeed, through their action on the renin-angiotensin system (RAS) and their local actions, ACE inhibitors have substantially improved the prognosis of patients with diseases over the entire continuum of CV disease, including HT, stable coronary artery disease, myocardial infarction (MI), and heart failure (HF), and have been applied specifically to prevent stroke, although also preventing diabetes and delaying or reducing renal dysfunction. The strength of available clinical data is such that guidelines developed for cardiologists by professional societies now recommend the use of ACE inhibitors for the management of HT, coronary and atherosclerotic vascular disease, MI, and HE Newer ACE inhibitors with pharmacological profiles differing from those of older agents have added to the ease of application and relative safety of these drugs both for reduction of symptoms and for improvement of outcomes. Although other agents modulating RAS can provide some overlapping pharmacological effects and important clinical benefits, ACE inhibitors remain unique in the range of their proven benefits, justifying their central role in the armamentarium of the CV specialist.