The expanding clinical indications for the use of angiotensin-converting enzyme (ACE) inhibitors during the past three decades to reduce cardiovascular morbidity and mortality across a broad spectrum of cardiovascular diseases has been the consequence of impressively productive interchanges between basic science and clinical medicine. In some areas, the initial discovery from animal investigations produced the hypothesis that were confirmed and expanded in patients with specific disease processes. In the development of ACE inhibitors, there are also important examples where an unexpected discovery from clinical trials spurred a host of laboratory investigations that uncovered novel mechanisms to underpin the clinical observations. Although developed as an antihypertensive agent, these effective interchanges termed "translational research" has collectively produced convincing data to demonstrate that ACE inhibitors can and should be used to slow progression of renal disease, prevent and treat heart failure, attenuate adverse left ventricular remodeling following myocardial infarction and improve prognosis, reduce atherosclerotic complications in patients with coronary artery disease and, even more recently, reduce the incidence of type II diabetes.