Low 25-hydroxyvitamin D levels are common in the general and HIV-infected populations alike. Defined as levels less than 30 ng/mL, suboptimal vitamin D is known to afflict over 70% of representative samples from each group in resource-rich countries with even greater prevalence in resource-poor regions of the world. In both those with and without HIV, dark skin, low vitamin D intake, exiguous exposure to sunlight, and season act as risk factors for suboptimal vitamin D levels. In those infected with HIV, antiretroviral therapy, particularly non-nucleoside reverse transcriptase inhibitors (NNRTIs), increase risk for low vitamin D as well. Furthermore, metabolic aberrations, including obesity and hyperlipidemia, and miscellaneous risk factors, such as advanced AIDS and substance abuse, have been linked to suboptimal vitamin D in those with HIV. While the skeletal and cardiovascular systems of HIV patients may be adversely impacted as a result of low levels, recent data have also linked low vitamin D to decreased CD4 counts, higher viral loads, and to critical end points including progression to AIDS events and death. More research is needed to confirm these potential consequences of low vitamin D in those with HIV and to discern the benefits of routine screening for and treatment of low vitamin D in this population.