The physiological mechanisms that control energy balance are reciprocally linked to those that control reproduction, and together, these mechanisms optimize reproductive success under fluctuating metabolic conditions. Thus, it is difficult to understand the physiology of energy balance without understanding its link to reproductive success. The metabolic sensory stimuli, hormonal mediators and modulators, and central neuropeptides that control reproduction also influence energy balance. In general, those that increase ingestive behavior inhibit reproductive processes, with a few exceptions. Reproductive processes, including the hypothalamic-pituitary-gonadal (HPG) system and the mechanisms that control sex behavior are most proximally sensitive to the availability of oxidizable metabolic fuels. The role of hormones, such as insulin and leptin, are not understood, but there are two possible ways they might control food intake and reproduction. They either mediate the effects of energy metabolism on reproduction or they modulate the availability of metabolic fuels in the brain or periphery. This review examines the neural pathways from fuel detectors to the central effector system emphasizing the following points: first, metabolic stimuli can directly influence the effector systems independently from the hormones that bind to these central effector systems. For example, in some cases, excess energy storage in adipose tissue causes deficits in the pool of oxidizable fuels available for the reproductive system. Thus, in such cases, reproduction is inhibited despite a high body fat content and high plasma concentrations of hormones that are thought to stimulate reproductive processes. The deficit in fuels creates a primary sensory stimulus that is inhibitory to the reproductive system, despite high concentrations of hormones, such as insulin and leptin. Second, hormones might influence the central effector systems [including gonadotropin-releasing hormone (GnRH) secretion and sex behavior] indirectly by modulating the metabolic stimulus. Third, the critical neural circuitry involves extrahypothalamic sites, such as the caudal brain stem, and projections from the brain stem to the forebrain. Catecholamines, neuropeptide Y (NPY) and corticotropin-releasing hormone (CRH) are probably involved. Fourth, the metabolic stimuli and chemical messengers affect the motivation to engage in ingestive and sex behaviors instead of, or in addition to, affecting the ability to perform these behaviors. Finally, it is important to study these metabolic events and chemical messengers in a wider variety of species under natural or seminatural circumstances.