The advent and uptake of effective antiviral therapies has transformed HIV/AIDS into a chronic manageable illness. The majority of Americans living with HIV are now ages 50 and older. Given the confluence of aging and HIV, chronic pain among older persons living with HIV/AIDS (PLWHA) has emerged as an area of clinical importance. Treatment of pain among this population is complex due to the prevalence of substance abuse and psychiatric illness in the population as well as the challenges of disentangling how inflammation associated with aging and HIV interact to predispose pain. Through a review of the extant literature we examine the complex associations between substance use, mental health, psychosocial issues, and chronic pain using a biopsychosocial framework in order to provide a means of addressing the agingchronic pain link in older PLWHA. Using this frame, we then consider treatment implications for the population.