According to estimates, 1.2 million Americans are infected with human immuno deficiency virus (HIV). Because of antiretroviral therapy, persons who have HIV infection or have progressed to AIDS are living longer. As a result, the likelihood that they will need critical care nursing is increasing. Unlike in years past, when these patients were often admitted because of the consequences of immunosuppression, today they are also being cared for in critical care units for other conditions associated with aging, other chronic health conditions, and trauma. When persons who have HIV disease or AIDS are admitted to the intensive care unit, nurses must be prepared to provide care, especially management of complexities associated with antiretroviral therapy. Therefore, this article examines critical care nurses' role in initiating and administering antiretroviral therapy in the intensive care unit and reducing the risk of drug interactions associated with the therapy.