Antiretroviral therapy (ART) is one of the major medical successes of the late 20th century. Effective ART results in indefinite viral suppression, restored immune function, improved quality of life, the near normalisation of expected lifespan, and reduced viral transmission. Despite the inherent potency of ART to suppress virus replication, treatment approaches have limitations; ART does not eliminate viral reservoirs, and needs lifelong adherence to expensive regimens that have potential short-term and long-term toxic effects. In 2010, more than 34 million people were estimated to be living with HIV, an increase of 17% over the past 10 years, and the number is expected to increase. Will we have enough resources worldwide to provide treatment and monitoring to all who need them? Even for those with access to ART, individual adherence is a big drawback. Additionally, despite virus control, HIV-associated complications persist, including a higher than normal risk of cardiovascular disease, cancer, osteoporosis, and other end-organ diseases. This increased risk might be due to the toxic effects of treatment or the consequences of persistent inflammation and immune dysfunction associated with HIV. Therefore, novel treatment approaches that eliminate persistent virus and do not need lifelong adherence to expensive and potentially toxic antiretroviral drugs are needed.