The clinical benefit of aggressive blood pressure (BP) control in reducing adverse cardiovascular and renal outcomes is well documented. However, a majority of patients with hypertension remain poorly controlled with monotherapy and require two or more agents to achieve their target BP levels. Patients with hypertension who also have diabetes or renal disease benefit from even lower BP targets, but may be more difficult to treat and require three or more drugs to achieve control. Using two or more drugs, each at lower doses, is usually more effective and less commonly associated with adverse effects than higher doses of a single drug. With the increasing prevalence of diabetes and renal disease, the treatment of hypertensive patients with multidrug combinations will become even more common. Knowing how specific combinations can be used effectively will be an important component of the treatment strategy for hypertension.