Several recent comparative trials in hypertension have reported that similar blood pressure reductions may not necessarily translate into similar reductions in risk for cardiovascular complications. Thus, the method used to lower blood pressure may be important. In the Antihypertensive and Lipid-Lowering Treatment To Prevent Heart Attack Trial (ALLHAT), low-dose chlorthalidone as the first-line drug was superior to doxazosin. The 25% higher risk for major cardiovascular events associated with doxazosin was attributed primarily to a doubling in the risk for heart failure. A meta-analysis of patients with type 2 diabetes mellitus suggested that despite achieving similar blood pressure reductions, angiotensin-converting enzyme inhibitors are superior to other antihypertensive drugs in reducing the risk for acute myocardial infarction and cardiovascular events, but not stroke. Although individual comparative trials have failed to show conclusively that calcium-channel blockers differ from other antihypertensive drugs, a meta-analysis that included all published trials concluded that calcium-channel blockers are inferior to other classes of drugs in reducing the risk for acute myocardial infarction and heart failure. These observations suggest not only that antihypertensive drugs may have important mechanisms of action apart from blood pressure lowering but also that effective treatment is not a matter of simply lowering blood pressure. These findings have potential implications for the regulatory approval of antihypertensive agents, revisions of treatment guidelines, the design of future randomized trials comparing different antihypertensive drugs and, most important, the selection of drugs for the treatment of hypertensive patients.