Peripheral lipodystrophy, central adiposity, hyperlipidaemia, insulin resistance, and diabetes mellitus, in varying constellations, are frequent complications of highly active antiretroviral therapy in HIV1-infected patients. The pathogenetic significance of protease inhibitors toxicity has been demonstrated by the partial reversal of metabolic disorders after switching to other antiretroviral regimens. The therapeutic and prognostic implications of these metabolic disorders are not yet clear. The dramatic improvements in the prognosis and quality of life of people with HIV since the introduction of highly active antiretroviral therapy call for evidence based concepts for the management of treatment-related metabolic disturbances.