Alpha-adrenergic receptors play an important role in the regulation of blood pressure (BP). There are 2 principal types of alpha receptors, alpha 1 and alpha 2, and both participate in circulatory control. Alpha 1 receptors are the classic postsynaptic alpha receptors and are found on vascular smooth muscle. They determine both arteriolar resistance and venous capacitance, and thus BP. Alpha 2 receptors are found both in the brain and in the periphery. In the brain stem, they modulate sympathetic outflow. Their function in the periphery is not yet fully understood, but they may contribute both to control of sympathetic tone and to local and regional blood flow. Drugs that enhance central alpha 2 activity, such as clonidine, guanfacine and the active metabolite of methyldopa, can significantly lower BP and are effective in the long-term control of hypertension, either alone or in combination with other drugs. While central alpha agonists, as a class, share a common pharmacologic mode of action, side effects, e.g., sedation and drowsiness, occur to different degrees with different drugs, and the individual agents also vary in terms of their propensity for causing withdrawal hypertension. The use of low-dose regimens or of newer drugs, such as guanfacine, with its longer half-life and duration of action, may reduce the likelihood of adverse reactions associated with this class of drugs.