Autonomic failure can be divided into peripheral and central dysfunction on the basis of pharmacologic characteristics of the disorders. Low plasma NE levels, impaired neuronal uptake, and adrenergic receptor supersensitivity distinguish patients with PAF from those with MSA, who have defective baroreflex modulation of blood pressure and CNS neurotransmitter dysfunction. An increased understanding of neurotransmitter metabolism and function in patients with chronic autonomic failure has led to a variety of rational therapeutic approaches. Much progress has been achieved in the management of orthostatic hypotension, the most disabling feature of autonomic dysfunction. Treatment of the parkinsonian features in MSA is limited by pharmacologic sensitivity and autonomic failure. Elucidation of the neurochemical and pharmacologic abnormalities in these disorders suggests new therapeutic avenues for the future.