Angiotensin-converting enzyme (ACE) inhibitors have been FDA-approved for treating refractory hypertension since 1981. Since then, clinical investigations support the benefits of ACE inhibition (ACE I) in pathologies like congestive heart failure, myocardial infarction, diabetes mellitus, chronic renal insufficiency, and atherosclerotic cardiovascular disease. Both, clinical trials and animal models of type I and type II diabetes have shown that hyperactivity of the angiotensin II signaling pathway contributes to the development of diabetes and its complications, and that blockade of the renin angiotensin system prevents new onset diabetes and reduces the risk of diabetic complications. Furthermore, ACE inhibitors are generally well tolerated and have few contraindications. This article describes ACE as a target molecule and gives an overview on the clinical evidence that supports the use of ACE inhibitors in diabetes.