Lipodystrophy comes in several forms, some involving the complete failure to develop adipose tissue and others with a partial absence in various bodily distributions. All appear to have a major genetic basis, and all involve a high frequency of lipoprotein disorders. High triglycerides and low high-density lipoprotein cholesterol are the usual findings that raise interesting questions as to how such abnormalities characteristic of obesity can be caused by genetic variants that produce a paucity of adiposity. We are learning to link some specific genetic variants that seem causal and to manage these disorders in more effective ways. We are joined by 3 experts who have been leaders in the study of the clinical presentation, genetics, abnormal physiology, and the management of lipodystrophy in recent years. They are Drs Abhimanyu Garg from the University of Texas Southwestern, Phillip Gorden of the National Institute of Diabetes, Digestive and Kidney Diseases, and Robert Shamburek of the National Heart, Lung and Blood Institute.