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Treatment with angiotensin\u2010converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) has been demonstrated to prevent atrial fibrillation and new\u2010onset diabetes, and provide cardiac, cerebral, and renal protection. Combination therapy with ACEIs and ARBs, compared with monotherapy, provides enhanced reno\u2010 and cardioprotection, although available data indicate that combination RAS blockade may be beneficial only in select patient groups, such as those with diabetes mellitus, chronic kidney disease, or heart failure (HF). In certain high\u2010risk patients, the use of ARBs provides comparable efficacy to that observed with ACEIs. The efficacy of these agents may stem from pleiotropic effects beyond blood pressure (BP) reduction. Several studies demonstrate achievement of clinical endpoints without significant effects on BP. 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