With ongoing improvement in antiretroviral therapy, mortality among HIV-infected persons has dramatically decreased. For HIV-infected persons who remain engaged in care on suppressive therapy, life expectancy approaches that of the general population. Additionally, we have seen increases in comorbidities traditionally associated with aging: diabetes, hypertension, dyslipidemia, ischemic heart disease, and osteoporosis. Vitamin D deficiency has also been identified as a highly prevalent entity among HIV-infected populations. The association of vitamin D deficiency with several of these comorbidities and its impact on immune function provide the impetus for well-designed studies to evaluate the impact of vitamin D supplementation on HIV disease and antiretroviral therapy. This review summarizes the role of vitamin D in several disease states that are prevalent among HIV populations, with a specific focus on bone health and the interactions with antiretroviral medications. © 2010 Springer Science+Business Media, LLC.