This chapter discusses the complications arising from involvement of the meninges, spinal cord, and muscles by the virus. Clinical features, diagnostic tests, and management of HIV-associated myelopathy, myopathy, and meningitis are discussed. The incidence of clinical HIV-associated myopathy has not been established in prospective studies, although on the whole it appears to be relatively uncommon. In contrast, electromyography is sensitive and specific in the diagnosis of myopathy. Early reports described two histological patterns of HIV-associated myopathy prior to the availability of antiretroviral agents. The percentage of ragged red fibers was reported to be correlated with the severity of clinical myopathy. The conclusion was that mitochondrial abnormalities were not specific to ZDV-associated myopathy. Corticosteroids may provide benefit in HIV-associated myopathy. While intravenous immunoglobulins may be an alternative option without risk of immunosuppression, there is only limited reported experience with their use in HIV-associated myopathy. Spinal cord dysfunction, muscle disease, and meningitis may occur associated with HIV infection. The precise pathogenic mechanisms are unclear, but in myelopathy and myopathy, indirect mechanisms are believed to be responsible. In HIV-associated myelopathy, symptomatic treatment is the mainstay of management. Corticosteroids and intravenous immunoglobulin therapy are used for the treatment of HIV-associated myopathy; the initiation of HAART without myotoxic agents may also provide benefit in those who are untreated.