In patients with hypertension, the primary goal is to reduce elevated blood pressure. All of the currently available and approved antihypertensive therapies are, by and large, equally efficacious. Some patient groups and individual patients may, however, respond differentially, and as a result one therapy may be more optimal than another. Overall, for uncomplicated hypertension and particularly for isolated systolic hypertension, diuretics should be considered for first-line therapy. However, comorbid conditions (which occur in > 50% of hypertensive patients) may prompt the need for a more ideal first-line therapy (eg, hypertension with diabetic nephropathy or with left ventricular dysfunction). Regardless, most patients with hypertension will require multidrug therapy to achieve the blood pressure goal, and an angiotensin converting enzyme (ACE) inhibitor may well be part of that therapy. Many going outcome trials comparing the newer therapies (such as ACE inhibitors) with diuretic-based therapy may redefine or clarify the use of different antihypertensive regimens.