Leptin signals the repletion of fat stores, acting in the CNS to permit energy utilization by a host of autonomic and neuroendocrine processes and to decrease feeding. While much recent research has focused on the leptin-regulated circuitry of the hypothalamic arcuate nucleus (ARC), the majority of brain leptin receptor (LepRb)-expressing neurons lie outside the ARC in other CNS regions known to modulate energy balance. Each set of LepRb neurons throughout the brain presumably mediates unique aspects of leptin action, and understanding the function for LepRb-expressing neurons throughout the brain represents a crucial next step in the study of energy homeostasis.