The treatment of HIV infection is a dynamic topic. More than 15 compounds, derived from three classes of antiretroviral drugs, are now available. A large number of clinical trials have determined the combinations that are optimal to use as first-line therapy; further investigations are needed to establish the value of simplified regimens (reduced number of doses and/or pills per day) in any attempt to increase the adherence of patients to therapy. In patients experiencing virological failure, assessment of adherence to treatment is helpful to determine the mechanisms of failure and to choose an alternative therapeutic option. The value of in vitro viral resistance evaluation by genotypic and/or phenotypic methods is currently being investigated. The value of therapeutic regimens available at the present time to treat HIV infection is hampered by their side effects. Metabolic toxicity has recently been identified as a major point of concern, and a better understanding of its mechanisms is urgently needed. Finally, in patients with long-term response to treatment, the value of passive immunotherapy to reduce the size of the viral reservoir and the effect of transient treatment interruption on specific immunological response have recently been investigated, but the first results are disappointing.