Strategies that interrupt the renin-angiotensin system, especially with angiotensin-converting enzyme (ACE) inhibition, reduce cardiovascular disease mortality and morbidity in high-risk persons such as those with the insulin resistance syndrome and diabetes mellitus. In the 1980s emphasis was placed on the renal protective effects of ACE inhibitors in patients with diabetes and proteinuria. During the past several years controlled clinical trials have demonstrated that ACE inhibition reduces cardiovascular disease (CVD) mortality and morbidity. This is especially important in patients in the United States, where 80% of excess mortality for diabetes mellitus is attributed to CVD. This article reviews the clinical trials in high-risk patients, especially those with diabetes, that shown beneficial CVD risk reduction with ACE inhibitors.