The objective of this review is to evaluate the role of fixed-dose triple-combination therapy for the management of hypertension. An assessment of clinical trials showed that half the patients with hypertension have uncontrolled blood pressure (BP), with underlying factors including therapeutic inertia and poor patient adherence. Many patients will require three antihypertensive agents to achieve BP goals, and current guidelines recommend combining drugs with complementary mechanisms of action. Three single-pill triple-combination treatments are available and each includes an agent affecting the renin-angiotensin-aldosterone pathway (either a direct renin inhibitor or an angiotensin II receptor blocker) in combination with a calcium channel blocker and diuretic. These triple-combination therapies consistently demonstrated significantly greater BP reduction relative to the component dual combinations, with BP reductions documented across a range of patient populations. Triple-combination treatments were well tolerated in all clinical trials reviewed. The use of single-pill, triple-combination antihypertensive therapy has been shown to be an effective, well-tolerated, and convenient treatment strategy that can help patients achieve BP control.