Skeletal muscle involvement may occur at all stages of human immunodeficiency virus (HIV)-infection, and represents the first manifestation of the disease in some patients. There have been many controversies about the classification of myopathies related to HIV infection. We usually classify muscle involvement in HIV-infected patients in one of the following categories: (1) HIV-associated myopathy, a myopathy that meets the criteria for polymyositis in a majority of patients, and those for acquired nemaline myopathy in some; (2) zidovudine myopathy, a reversible mitochondrial myopathy; (3) the HIV-wasting syndrome and other AIDS-associated cachexias; (4) opportunistic infections and tumoral infiltrations of skeletal muscle; (5) vasculitic processes and iron pigment deposits. Immunohistology for major histocompatibility complex class I antigen and the histochemical reaction for cytochrome C oxidase are helpful in correctly classifying a myopathy as HIV polymyositis or zidovudine myopathy respectively. Studies of circulating levels and tissue expression of cytokines in HIV-infected patients have yielded new insights into the pathogenesis of the various AIDS-associated muscle disorders.