Recent advances in the understanding of the molecular basis of genetic lipodystrophies have promoted understanding of how adipose tissue disorders can cause the metabolic syndrome and its complications. These discoveries hold promise for elucidating pathways and mechanisms by which common disorders of obesity cause metabolic complications. Novel therapeutic approaches for patients with lipodystrophies also may have implications for treatment of the metabolic syndrome in patients with regional adiposity. This article reviews these recent advances in our knowledge of the clinical features, metabolic abnormalities, and pathogenetic or other bases of various types of lipodystrophies.