Combined antiretroviral therapy has surprisingly improved prognosis of patients infected with human immunodeficiency virus type 1 (HIV-1). Nobel antiretrovirals with potency and activity, dosing convenience, and tolerability have been approved since 1996. However, side effects have been reported with all antiretroviral agents and are the common reasons for switching or discontinuing therapy and for poor adherence. While some frequent adverse effects (e.g., diarrhea, eruption, abnormal dream, jaundice, bone marrow suppression) were reported during clinical trials, some less frequent side effects (e.g., lactic acidosis) and long-term adverse drug reactions (e.g., lipodystrophy, hyperlipidemia) were not identified until the antiretrovirals had been prescribed for years. In this paper, the common adverse effects of major antiretroviral agents, potential preventive measures, and suggested management strategies are described.