With the recent development of potent new antiretroviral therapies, the management of HIV infection has become increasingly complex. There are now 12 antiretroviral drugs approved for use in the management of HIV infection, with several more in the advanced stages of clinical development. Staying current with this rapidly changing area of medicine is a challenge to clinicians caring for HIV-infected patients. This review provides an overview of HIV pathogenesis and discusses the basic principles of therapy. These principles, developed recently by the U.S. Department of Health and Human Services, provide a practical framework to rapidly incorporate new developments into clinical practice. Each of the three classes of antiretroviral therapies is then explained, focusing on the practical management of side effects, drug interactions, and viral resistance. The antiviral activity and clinical efficacy of each therapeutic class is reviewed, with an emphasis on applying current results to clinical decision making. Finally, recently published treatment guidelines are reviewed.