Low bone mineral density (BMD) is common in those with HIV, associated with higher bone turnover and a higher prevalence of fractures. This review explores low BMD in HIV, focusing on underlying mechanisms and relationships between low BMD and HIV infection, immune dysfunction, and antiretroviral therapy (ART). Greater reductions in BMD accompanying reductions in HIV viremia at initiation of first-line or second-line ART suggest an important role for immune- or viral-mediated mechanisms in its pathogenesis. As bone metabolism is part-regulated by T cells and B cells, we propose that earlier initiation of ART at higher CD4 T-cell counts may attenuate BMD loss by abrogating immune- and viral-mediated disturbances in bone metabolism that accompany ART initiation. Further pathogenesis-based research is required in this field, focusing on the complex interaction between virus, immune system, ART, and bone metabolism.