Persons over age 50 are not only aging with human immunodeficiency virus (HIV) infection but also represent a high proportion of new HIV infections. Neuropsychiatric symptoms, including depression, cognitive impairment, and substance abuse, are very common in individuals infected with HIV. However, there is little understanding of the relationship between these HIV-related comorbid conditions in newly infected elderly patients compared to uninfected elderly and those who have survived after 20 years of HIV/AIDS. We summarize the current theories and research that link aging and HIV with psychiatric illnesses and identify emerging areas for improved research, treatment, and patient care.