Highly active antiretroviral therapy (HAART) can significantly alter the clinical course of patients infected with HIV. Unfortunately, effective lifelong HAART may not be a practical or achievable goal because of toxicities, cost, development of viral resistance and patient compliance issues. Immune-based therapies (IBTs) that target the host immune system may serve as rational additions to our current antiretroviral strategies. Investigations into IL-2 have culminated in two large Phase III clinical trials. Multiple therapeutic vaccine candidates are in various phases of investigation. In addition, gene therapy has been proposed as a potential treatment for HIV and Phase I trials are ongoing. Although IBTs are being investigated on many fronts, they remain difficult to study due to a lack of validated surrogate end points.