Examination of the large-scale drug-versus-drug trials suggests that the initial drug choice is of token importance and that better blood pressure control is the primary determinant of superior outcomes. In pooled analyses, the achieved blood pressure is similar for older and less expensive drugs, such as thiazide-type diuretics, and for newer and more costly agents, such as angiotensin-converting enzyme inhibitors, -angiotensin-receptor blockers, and calcium-channel blockers. If blood pressure--independent differences favoring one antihypertensive drug class over another truly exist, they have been singularly difficult to uncover with any consistency. Considering that multidrug therapy is required in the majority of patients with hypertension, the debate as to which drug class is best to start with is moot, in that the clinician is now more called upon to decide the best combinations of drugs and not the best monotherapy.