The criminal justice system bears a disproportionate burden of the HIV epidemic. Continuity of care is critical for HAART-based prevention of HIV-related morbidity and mortality. This paper describes four major challenges to successful management of HIV in the criminal justice system: relapse to substance use, homelessness, mental illness, and loss of medical and social benefits. Each of these areas constitutes a competing priority upon release that demands immediate attention and diverts time, energy, and valuable resources away from engagement in care and adherence to HAART. Numerous gaps exist in scientific knowledge about these issues and potential solutions. In illuminating these knowledge deficits, we present a contemporary research agenda for the management of HIV in correctional systems. Future empirical research should focus on these critical issues in HIV-infected prisoners and releasees while interventional research should incorporate evidence-based solutions into the criminal justice setting.