For decades, increasingly sophisticated methods have been designed to address the problem of the involvement of the brain in the physiology of energy homeostasis and the pathogenesis of obesity. A vast number of experimental observations have been made from novel genetic and physiologic approaches that allowed the identification of metabolic hormones and their relationship to key peptidergic systems in the brain. Although the central integration of afferent signals reflecting acute and chronic energy requirements is becoming clearer, the blueprint of the central regulation of energy expenditure is not known. This review offers a look at central neuronal circuitries that are implicated in metabolism regulation and strongly suggests that without a blueprint, attempts to intervene and control energy balance will remain futile.