When patients with rheumatic or other immune-mediated diseases develop acute or chronic neurologic problems, several etiologic possibilities need to be considered. Many of the anti-inflammatory or immunosuppressive medications used to treat these disorders have direct adverse effects on the nervous system, including effects that overlap with neurologic complications of the patient's underlying disorder. Neuromuscular syndromes (peripheral neuropathy, myasthenia gravis, or myopathy) can complicate therapy with corticosteroids, antimalarials, gold, D-penicillamine, colchicine, cyclosporine, and FK506. A large number of anti-inflammatory and immunosuppressive medications can produce altered mental status and other central nervous system manifestations. Such drugs include corticosteroids, nonsteroidal anti-inflammatory drugs, methotrexate, antimalarials, gold, intravenous immunoglobulin, chlorambucil, cyclosporine, FK506, OKT3, and type I interferons. Aseptic meningitis is associated with use of nonsteroidal anti-inflammatory drugs, intravenous immunoglobulin, and OKT3. These and other neurologic adverse effects are the focus of this review.