The last decade witnessed a dramatic increase in knowledge concerning regulation of body weight and obesity. According to recent concepts constancy of body weight is a side product of regulatory events which ensure constant glucose fluxes to the brain. Within these control systems glucocorticoids and melanocortins play a fundamental role at several sites. The melanocortin neurons in the arcuate nucleus are important mediators of the feedback effects of leptin and insulin. Glucocorticoid and mineralocorticoid receptors in hippocampal neurons are crucial as they define the balance between glucose allocation processes and food intake. Thereby, the hippocampal structures determine the setpoint for bodyweight regulation. Novel approaches to treatment of obesity must aim at manipulating these brain structures.