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 of the hypothalamus 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 body weight regulation. A modulation of these brain structures by intranasal administration of melanocortin and inhisulin has been shown to reduce body weight and body fat mass in humans. So the manipulation of weight-regulating centers in the brain opens a novel approach to a pathogenetically based treatment of obesity.