Antiretroviral (ARV) medications have been in clinical use for 20 years in the treatment of HIV and our knowledge about the safety of these medicines continues to grow. The potential side effects of ARVs can be either short term, such as hypersensitivity reactions, drug-induced hepatitis, anemia and lactic acidosis, or long term, including dyslipidemia, cardiovascular disease, lipoatrophy, lipohypertrophy and diabetes. In general, the safety profile of ARVs is improving as new combinations of medicines and newer medicines are introduced into clinical practice. However, it is crucial that vigilance be maintained in monitoring for side effects, particularly in resource-limited settings.