Combination antiretroviral therapy (cART) is highly effective at preventing morbidity and mortality due to infection with human immunodeficiency virus (HIV), but does not eradicate the virus. Consequently, cART must be administered life-long. Recent progress has stimulated research towards a cure of HIV infection. Approaches under investigation include hematopoietic stem cell transplantation, latency reactivating agents, immune based therapies, and cell-based therapies. Each of these approaches carries potential risks that must be weighed against the availability of safe and effective cART. Balancing the risks and benefits of this research poses unique challenges to potential study participants, clinicians and investigators.