Introduction of HAART (highly active antiretroviral therapy) has resulted in dramatic reductions in AIDS-related opportunistic complications and death. We have faced, however, severe complications due to HAART such as lactic acidosis and lipodystrophy syndrome. Regimens currently employed in the treatment may be complex, require multiple drugs to take, difficult to tolerate owing to adverse effects, and decrease level of quality of life in some patients. Decisions about when and with what to initiate HAART must take into account the risk-benefit ratio associated with the therapy. In this article, issues that must be considered in determining timing of initiation and choice of anti-retroviral drugs are discussed.