Human lipodystrophies represent a group of diseases characterized by altered body fat amount and/or repartition. Most forms of lipodystrophies are associated with metabolic alterations such as insulin resistance, diabetes and dyslipemia, leading to diabetic complications, increased cardiovascular risk or liver steatosis. Lipodystrophies can be classified as genetic or acquired, generalized or partial. Genetic forms such as Berardinelli-Seip syndrome or partial familial lipodystrophies are uncommon and acquired forms are much more frequent. Beside the rare Lawrence or Barraquer-Simons syndromes, the main forms of acquired lipodystrophies are those observed in HIV-infected people treated with antiretroviral therapies or in people exposed to an endogenous or an exogenous hypercortisolism. The treatment of lipodystrophies is difficult. Lifestyle modifications (e.g., specific diet, physical training) may be helpful but are usually insufficient. Associated metabolic disorders should be treated as soon as possible with insulin sensitizers, insulin and lipid lowering drugs. New therapies such as leptin have been proven to be helpful in some genetic or acquired forms of lipodystrophy.