Although the brain is capable of sensing a variety of nutrient signals, it must integrate those signals and generate an appropriate behavioral response. The Central Melanocortin System, composed of proopiomelanocortin (POMC)/alpha-MSH-producing neurons originating in the arcuate nucleus of the hypothalamus or the nucleus of the solitary tract, is perfectly positioned to integrate nutritional signals of both peripheral and central origin. Several neural systems have been implicated as downstream effectors of melanocortin actions; however, the organization and order of activation of those systems is only now becoming understood. Using pharmacological approaches in whole animal models, we have confirmed the association of the Central Melanocortin System with downstream activation of central corticotropin releasing hormone (CRH) receptors and the central oxytocin system. Furthermore, we have delineated the organization of this essential circuit, in that activation of CRH receptors occurs after stimulation of POMC neurons, which in turn leads to the activation of the central oxytocin system. Interestingly, although this circuit appears to be important for the regulation of feeding behavior, an alternative and as yet unknown circuit underlies the cardiovascular actions of the central melanocortin system. These findings may have important implications for the pathogenesis of obesity and its associated complications, including obesity-associated diabetes and hypertension.