Musculoskeletal manifestations of the human immunodeficiency virus (HIV) are common and are sometimes the initial presentation of the disease. Knowledge of the conditions affecting muscle, bone, and joints in HIV-infected patients is essential for successful management. Myopathies may be caused by pyogenic infection (eg, pyomyositis), idiopathic inflammation (eg, polymyositis), or drug effect (eg, AZT myopathy). Characteristic skeletal infections, such as tuberculosis and bacillary angiomatosis, require a high index of suspicion for accurate diagnosis. Neoplastic processes, such as non-Hodgkin's lymphoma and Kaposi's sarcoma, occur more frequently as the immune system deteriorates. Inflammatory and reactive arthropathies are more prevalent in HIV-positive than HIV-negative individuals and include Reiter's syndrome, psoriatic arthritis, HIV-associated arthritis, painful articular syndrome, acute symmetric polyarthritis, and hypertrophic osteoarthropathy. Patients with atypical musculoskeletal complaints and a suspected history of exposure should be tested for HIV.