The lipodystrophy syndromes are rare disorders characterized by the loss of adipose tissue. The loss of fat tissue can have genetic, immune, or infectious/drug-associated causes. With the extent of fat loss metabolic complications, such as insulin resistance, diabetes mellitus, hypertriglyceridemia, and fatty liver increase in severity. Lipodystrophies can be divided into two subtypes: familial and acquired. Causative mutations have recently been identified in one form of familial lipodystrophy as well as in one form of acquired lipodystrophy. Several mouse models might help understanding the development of these syndrome. In this review article, the recently introduced classification of lipodystrophy syndromes is presented as well as new insights into pathogenesis and therapeutic strategies.