Lipodystrophy (LD) is a well-recognised clinical syndrome of peripheral fat atrophy and central adiposity, often associated with laboratory abnormalities such as dyslipidemia and glucose intolerance, and probably linked to insulin resistance. The long-term consequences of LD and its potential association with cardiovascular disease remain unknown. The visceral fat accumulation is characterised by the increased, abundant secretion of a number of peptides such as leptin, insulin-like growth factor (IGF), adiponectin and the recently reported resistin and visfatin hormones. Elevated resistin and tumour necrosis factor (TNF-alpha) levels and low levels of adiponectin secretion may have implications for the risk of development of type 2 diabetes and cardiovascular disease. LD is observed not only in rare autosomal syndromes, but also in patients positive for the human immunodeficiency virus (HIV) who have been treated with protease inhibitors. Both the origin of LD and its treatment deserve more attention and further research in clinical settings.