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Abstract: This chapter presents a practical and clinically oriented approach to chronic musculoskeletal pain in HIV, recognizing that such symptoms may be related to a wide variety of underlying disorders. It reviews the epidemiology of musculoskeletal pain in HIV and its potential mechanisms and offers an approach to diagnosis. HIV and antiretroviral therapy (ART) may have direct effects on the musculoskeletal system. The chapter describes the treatment approaches specific to the disorders. It also addresses three of the most common and challenging chronic musculoskeletal pain syndromes: low back pain, widespread pain including fibromyalgia, and myofascial pain syndrome. Although management of chronic musculoskeletal pain in HIV will be tailored to the individual, general principles include combination of pharmacological interventions such as nonsteroidal anti-inflammatory drugs (NSAIDS) or serotonin-norepinephrine reuptake inhibitors (SNRIs), with physical modalities designed to prevent or reverse deconditioning, and psychological modalities designed to enhance coping.