More than 25 antiretroviral drugs and fixed-dose combinations have been approved by the US Food and Drug Administration for the treatment of human immunodeficiency virus (HIV) infection in the 2½ decades since zidovudine (ZDV) became the first drug approved for this purpose. These drugs now constitute 6 different classes, including nucleoside and nucleotide reverse-transcriptase inhibitors (NRTIs), nonnucleoside reverse-transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), integrase strand-transfer inhibitors, fusion inhibitors, and entry inhibitors. When used in appropriate combinations (usually 2 NRTIs plus a third drug from another class), these drugs achieve sustained suppression of viral replication, resulting in the arrest of disease progression and reconstitution of immune function. Such combination antiretroviral therapy (cART) has resulted in dramatic declines in HIV-associated morbidity and mortality wherever treatment is accessible.1,2