Highly active antiretroviral therapy (HAART) has changed the natural history of HIV infection, but the presence of adverse events may limit its efficacy. Nucleoside reverse transcriptase inhibitors can cause mitochondrial toxicity and anemia, non-nucleoside reverse transcriptase inhibitors are associated with rash and central nervous system disturbance; protease inhibitors elicit gastrointestinal adverse effects and metabolic abnormalities including lipodystrophy syndrome, hyperlipidemia and insulin resistance. These complications have the potential to increase morbidity and mortality significantly in those requiring long-term treatment of HIV-infection. The presence of such abnormalities also has an impact on adherence to treatment. Besides providing health benefits, HAART may have a negative impact on patients' quality of life. Identifying and treating these complications has important implications for patient survival.