Hypertension is a leading contributor to the burden of cardiovascular disease. The importance of lowering blood pressure (BP) to reduce the risk of cardiovascular events has been demonstrated in numerous clinical trials. Most patients require combination antihypertensive therapy utilizing agents from complementary drug classes to achieve BP goals. A calcium channel blocker (CCB)/angiotensin receptor blocker (ARB) combination is a rational approach for such an antihypertensive strategy. Benefits of CCB/ARB combination therapy include additive BP-lowering effects and lower incidences of adverse events (AEs). These agents demonstrate benefits associated with their respective drug classes. The ARBs confer stroke protection, renal protection, and tolerability similar to placebo, without dose-related symptomatic and metabolic AEs, while CCBs are beneficial in reducing stroke and treating angina and cardiac ischemia. The efficacy of this combination has been recently investigated in clinical trials wherein amlodipine was combined with olmesartan medoxomil or valsartan. This article discusses the rationale for using CCB/ARB combinations in patients with hypertension.