Immune-mediated disorders of each of the structural subdivisions of the nervous and neuromuscular system have been described. Despite the immune privilege of the central nervous system, and to a lesser extent the peripheral nervous system, immune dysregulation is not uncommon. Environmental, genetic, and immunologic factors have been postulated to be involved in the development of these disorders. Major immune-mediated neurologic diseases of the central nervous system include multiple sclerosis and acute disseminated encephalomyelitis. Immune-mediated diseases of the peripheral nervous system include myasthenia gravis, Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, idiopathic polymyositis, dermatomyositis, and inclusion body myositis. Some of these disorders, such as myasthenia gravis and certain forms of acute inflammatory demyelinating polyneuropathy, are clearly autoimmune in nature, whereas the immune system plays an important role in pathogenesis in others. Understanding the immune mechanisms of disease and uncovering potential therapeutic targets are essential for the design of new treatments. The epidemiology, pathogenesis, diagnostic criteria, and current therapeutic approaches to the major neuroimmunologic diseases are reviewed. (J Allergy Clin Immunol 2003;111:S659-68.)