Cortisol in obesity is a much-studied problem. Previous information indicates that cortisol secretion is elevated but that circulatory concentrations are normal or low, suggesting that peripheral disappearance rate is elevated. These studies have usually not taken into account the difference between central and peripheral types of obesity. Recent studies using saliva cortisol have indicated that the problem is complex with both high and low secretion of cortisol, perhaps depending on the status of the function of the hypothalamic-pituitary-adrenal gland axis. A significant background factor seems to be environmental stress. The results also suggest that the pattern of cortisol secretion may be important. Other neuroendocrine pathways are also involved, including the central sympathetic nervous system, the gonadal and growth hormone axes, and the leptin system. In concert, these abnormalities seem to be responsible for the abnormal metabolism often seen in central obesity. Several associated polymorphisms of candidate genes may provide a genetic background. Cortisol conversion to inactive metabolites may be a factor increasing central signals to secretion and may add to the increased secretion of cortisol induced by centrally acting factors. Perinatal factors have been found to be involved in the pathogenesis of obesity and its complications. The mechanism involved is not known, but available information suggests that programming of the hypothalamic-pituitary-adrenal axis may be responsible.