Various factors interfere wtih proper access to and initiation of antiretroviral therapy in the HIV-infected homeless population, and it is important for health care providers to explore and address barriers to obtaining antiretroviral therapy and to foster a trusting relationship before offering therapy so that its success may be maximized. Patient education about the multifaceted aspects of antiretroviral therapy is a crucial component of care. Care providers should aggressively identify barriers to adherence and facilitate patient adherence by using multiple strategies, establishing solid lines of communication within the provider team, bringing program services to patients, and educating ancillary service providers about adherence. Comanagement of antiretroviral therapy requires an interdisciplinary approach that includes case managers, mental health and substance abuse counselors, shelter providers, medical specialists, and parole/probation officers. More research is needed to understand the complexities of HIV/AIDS within the homeless population and to develop treatment interventions.