Hypertension affects approximately 73 million individuals in the United States. Clinical studies have shown that antihypertensive therapy can reduce blood pressure (BP) and the risk of cardiovascular events. However, the majority of patients with hypertension do not achieve the recommended BP goal of < 140/90 mm Hg (or < 130/80 mm Hg for patients with diabetes) with antihypertensive monotherapy, and require therapy with 2 or more antihypertensive agents. Combination therapy utilizes antihypertensive agents from different drug classes, which act via distinct pharmacologic mechanisms to improve overall efficacy and tolerability. Although combination therapy is superior to monotherapy in achieving BP goals across the entire spectrum of hypertension, the proportion of patients achieving the recommended BP goal can be further improved by the use of new antihypertensive drug combinations. The beneficial antihypertensive characteristics of both angiotensin receptor blockers and calcium channel blockers suggest that combining these classes may result in a highly efficacious antihypertensive therapy with regard to both activity and safety when used as a fixed-dose combination. In particular, a fixed-dose combination of olmesartan medoxomil plus amlodipine besylate has been demonstrated to be an efficacious antihypertensive combination due in part to the benefits associated with each of these agents within their respective drug classes.