Pain is the most common reason for the hospitalization of people with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS). The epidemiology of this disease and limitations of available therapies suggest that HIV/AIDS pain will be a treatment challenge within and beyond the perioperative realm for some time to come. This paper examines HIV/AIDS pain by major body systems. Suggestions are provided for pain assessment in HIV/AIDS patients. Both pharmacological and nonpharmacological treatment of pain in this complex population are described.