Treatment of patients at high risk for developing cardiovascular disease aims at controlling blood pressure, optimizing blood glucose levels, and providing renoprotection. Chronic kidney disease (CKD) and diabetes mellitus are prevalent causes of cardiovascular disease owing to associations with major cardiovascular risk factors, such as hypertension, and they are substantial health burdens. Even mild-to-moderate CKD and prehypertension increase cardiovascular risk. First-line agents for reducing cardiovascular risk are inhibitors of the renin-angiotensin system: angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs). In clinical trials, treatment of high-risk patients with ACE inhibitors and ARBs delays or prevents the onset of diabetes and prevents progression of renal disease and cardiovascular events, including cardiovascular mortality. Current evidence indicates that the clinical efficacy of these end points includes effects that may be beyond blood pressure reduction.