Antiretroviral toxicity is an increasingly important issue in the management of HIV-infected patients. With the sustained major declines in opportunistic complications, HIV infection is a more chronic disease, and so more drugs are being used in more patients for longer periods. This review focuses on the pathogenesis, clinical features, and management of the principal toxicities of the 15 licensed antiretroviral drugs, including mitochondrial toxicity, hypersensitivity, and lipodystrophy, as well as more drug-specific adverse effects and special clinical settings.