Body homeostasis is predominantly controlled by hormones secreted by endocrine organs. The central nervous system contains several important endocrine structures, including the hypothalamic-pituitary axis. Conventionally, neurohormones released by the hypothalamus and the pituitary gland (hypophysis) have received much attention owing to the unique functions of the end hormones released by their target peripheral organs (e.g., glucocorticoids released by the adrenal glands). Recent advances in mouse genetics have revealed several important metabolic functions of hypothalamic neurohormone-expressing cells, many of which are not readily explained by the action of the corresponding classical downstream hormones. Notably, the newly identified functions are better explained by the action of conventional neurotransmitters (e.g., glutamate and GABA) that constitute a neuronal circuit. In this review, we discuss the regulation of appetite and metabolism by hypothalamic neurohormone-expressing cells, with a focus on the distinct contributions of neurohormones and neurotransmitters released by these neurons. Metabolism: Dual function for neurohormone-producing cells in the brain Signaling molecules produced by the brain's hypothalamus function both as neurotransmitters (within the central nervous system) and hormones (throughout the rest of the body) to regulate appetite and metabolism. Jong-Woo Sohn and colleagues from the Korea Advanced Institute of Science and Technology in Daejeon, South Korea, summarize the well-established ways in which certain hypothalamic cells interact with parts of the pituitary gland in the brain to control the activity of hormones involved in feeding behaviors and energy balances.The same cells can also impact appetite and metabolism in non-hormonal ways. New research has shown that neurohormone-producing cells in the hypothalamus can form connections with appetite-associated neurons and communicate via neurotransmitters. A deeper understanding of this process could lead to new therapies for obesity, diabetes and other metabolic disorders.