The observation that different patterns of adipose tissue distribution are associated with different metabolic abnormalities, has recently given new impetus to research in obesity. Due to several methodologic problems, however, many aspects of regional excess of adipose tissue are still poorly understood. Among them, the causes and the metabolic consequences of regional adiposity are particularly important. Heterogeneity in adipose tissue distribution may be determined by a combination of genetic and hormonal causes. Both factors may determine differences in metabolism of various adipose tissue compartments primarily by regulating LPL production, storage and release of triacylglycerols, and aromatization of androgens. Furthermore, changes in adipocyte sensitivity to hormones such as, sex steroids, glucocorticoids, insulin and adrenergic hormones may also regulate fat distribution in various adipose tissue compartments. The metabolic heterogeneity of adipose tissue from various compartments, particularly the differences between the "portal" and subcutaneous adipose tissues, may account for several metabolic abnormalities associated with "upper body adiposity". However, no direct evidence is available to confirm this hypothesis. Recent advances in the methodology to study adipose tissue distribution (mainly CT and MRI) may provide the necessary tools to evaluate the true impact of adiposity in various compartments on intermediary metabolism and to identify a "morbid" adipose tissue compartment. These observations may help in designing better therapeutic strategies targeted towards regional adiposity and its metabolic complications.