As the AIDS epidemic progresses, the number of ED patients with HIV-related illness will continue to increase. As reviewed in this article, much of the existing clinical research in HIV-related illness has an impact on the diagnostic and management issues that arise in the ED. Many of the patterns of disease, subtleties of diagnosis, and therapies unique to AIDS patients have already been greatly elucidated. However, as the recognition of this disease goes into only its second decade, many questions remain. Further studies are needed, for example, to improve physician assessment of HIV risk, to further identify discriminators of PCP and bacteremia, and to optimize strategies for disposition and outpatient management. In the future, in the areas of research and clinical care, emergency medicine will play an increasing important role in the front-line attack on this modern epidemic.