Hypertension treatment should focus on achieving blood pressure (BP) of < 140/90 mm Hg in most patients and < 130/80 mm Hg in patients with diabetes. Lifestyle modifications play a central role in therapy and should be the first line of treatment in all patients. However, long-term lifestyle changes are rarely achieved and pharmacotherapy is required. The selection of an optimal regimen for each patient will depend on comorbid conditions. Most patients will require combination therapy with ≥ 2 antihypertensive agents to control their BP. The most useful combinations employ drugs from different classes with complementary mechanisms of action, producing additive or synergistic BP reduction with minimal adverse events.