Twenty individual antiretroviral drugs and two coformulation products are approved by the US Food and Drug Administration for the treatment of HIV-infected individuals. Many of these drugs have been associated with allergic/hypersensitivity reactions to varying degrees. The antiretroviral drugs that are most commonly associated with these types of reactions are abacavir, all of the nonnucleoside reverse transcriptase inhibitors, and amprenavir. Trimethoprim-sulfamethoxazole, although not an antiretroviral drug, is extensively used for the treatment and prophylaxis of HIV-related opportunistic infections and has been associated with a significant rate of adverse reactions. The authors provide an overview of these drug-related reactions and discuss their pathogenesis and management.