Although the social, economic, and political dimensions of the HIV/AIDS epidemic have been studied in considerable depth, the relationship between HIV/AIDS and its environmental causes and consequences remains largely unexplored. We reviewed the evidence of interactions between ecosystem health and the HIV/AIDS pandemic. We hypothesized a syndemic between environmental degradation and HIV/AIDS; they exhibit bidirectional, self-reinforcing interactions. We have presented a syndemic framework detailing multiple synergistic relationships. This framework hinges on the vulnerability of populations as the linchpin between the pandemic and environmental health. A coherent research and practice agenda for addressing the syndemic that focuses on the 2 issues as not only concurrent but also intertwined phenomena is urgently needed.