Infection with human immunodeficiency virus (HIV) is associated with marked disturbance of metabolism affecting the metabolism of carbohydrates, fats and proteins. In the first decade of clinical experience of HIV, the primary clinical manifestation of such disturbed metabolism was wasting. Such wasting was often severe and contributed significantly to the morbidity and mortality of AIDS. Mechanistic studies demonstrated that in addition to the effects of altered intermediary metabolism, reduced food intake played a major role in the causation of AIDS-related wasting. More recently, potent anti-retroviral drugs have dramatically changed the clinical consequences of HIV infection. Wasting has become far less frequent among infected patients and occurs in only a small percentage of subjects on effective anti-retroviral therapy. However, a new constellation of metabolic syndromes has become apparent characterized by altered body fat distribution (‘lipodystrophy’), lactic acidosis and evidence of mitochondrial dysfunction. The mechanistic basis for such syndromes is currently unclear, but is the subject of ongoing research.