Orthostatic hypotension is the most incapacitating symptom of autonomic failure. This disorder occurs with both central autonomic neurodegenerative disorders, such as multiple system atrophy and Parkinson's disease, and peripheral autonomic disorders, such as the autonomic peripheral neuropathies and pure autonomic failure. The hallmark of both central and peripheral causes of neurogenic orthostatic hypotension is the failure to release norepinephrine appropriately upon standing. Patient education is the cornerstone of management. There are several measures that can be implemented to improve orthostatic tolerance prior to pharmacological intervention. Plasma volume expansion is essential to improve orthostatic tolerance, and fluid and sodium chloride intake should be increased. Most patients can be treated successfully with volume expansion or fludrocortisone or both in combination with a sympathomimetic agent. Desmopressin acetate and erythropoietin are useful supplementary agents in patients with more refractory symptoms. There are rare patients who will require additional agents to treat their symptoms. A small group of patients remain refractory to all therapeutic modalities.