Community-based organizations (CBOs) are integral to achieving the goal of Ending the HIV epidemic (EHE). Their familiarity with and proximity to communities position them to effectively implement strategies necessary to address determinants of health through their formal and informal medical and social services. However, structural inequities have contributed to the demise of many organizations that were instrumental in early responses to the HIV epidemic. We define structural inequities for HIV CBOs as systems in which policies, institutional practices, organizational (mis)representations, and other norms work to produce and maintain inequities that affect CBOs' ability to survive and thrive. In this discussion, we describe the organizational threats to grassroots HIV CBOs and the risks to livelihood and longevity, including examples. The invaluable role of HIV CBOs in EHE and their role in responding to existing and novel infectious diseases like COVID-19 should not be overlooked. Recommendations to promote structural equity are offered. (Am J Public Health. 2022;112(3):417-425. https://doi.org/10.2105/AJPH.2021.306688).