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The goal of antihypertensive treatment is to reduce both blood pressure and other risk factors for cardiovascular disease. There are currently six major classes of antihypertensive drugs that are available for the initial lowering and maintenance of blood pressure, including β-blockers, α-adrenoceptor blockers, calcium channel blockers, diuretics, angiotensin-converting enzyme inhibitors and angiotensin-II receptor antagonists. All these classes of antihypertensive drugs are equally effective in reducing high blood pressure. To select the right antihypertensive drug, characteristics other than efficacy should be used to distinguish the different classes. According to the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure, the selection of initial antihypertensive drug should consider patient risk-factor profile and co-morbidity, as well as the safety and tolerability profile of the drug. When these factors are considered, an effective and well-tolerated drug regimen can be tailored to an individual patient. An initial drug regimen should consist of a low dose of a long-acting, once-daily drug that is titrated upward if blood pressure is not adequately controlled. Low-dose combinations of two antihypertensive drugs may also be considered. Results from comparative studies with different classes of antihypertensive drugs suggest that different populations of patients, such as those with diabetes, left-ventricular dysfunction, or lipid disorders, may benefit from taking different antihypertensive drugs.