Each of the 3 traditional classes of antiretroviral drugs (nucleoside/nucleotide reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors, and protease inhibitors [PIs]) has characteristic sets of toxicities that are not found with the other drug classes. On the other hand, lipodystrophy, which was thought to be specific to PIs, is now known to be common to all 3 classes of drugs. An understanding of the drug-specific, class-specific, and general toxicities and side effects of antiretroviral drugs will help the clinician tailor treatment regimens to individual patients.