OBJECTIVE: To review recent advances in the management of persons infected with HIV. DATA SOURCES: A MEDLINE search (March 2003-February 2006) was done to identify recent articles on antiretroviral therapy research, adverse effects, and investigational products. Abstracts and programs of major HIV conferences, held from January 2003 to June 2005, were also reviewed for relevant material. STUDY SELECTION AND DATA EXTRACTION: Studies and observations conducted with either recently approved or investigational products were selected for inclusion, with conference abstracts primarily used. Excluded were topics covered in recent publications in The Annals. DATA SYNTHESIS: New modalities for treating HIV, including the CXCR4 and CCR5 receptor inhibitors, have so far shown promise in trial. Tipranavir, a recently approved protease inhibitor, has been shown to be effective in highly resistant patients, but may be unable to be combined with other protease inhibitors. Once-daily emtricitabine and tenofovir have shown superiority compared with lamivudine and zidovudine as backbone nucleoside analogs for combination antiretroviral therapy. Pharmacokinetic considerations for age, gender, race, and which agents are being discontinued have emerged. CONCLUSIONS: Much progress has been made in the treatment of HIV infection. Tolerability and adherence remain major obstacles to optimizing regimen longevity.