This issue of the American Journal of Physiology: Endocrinology and Metabolism contains the first three in a series of review articles dealing with metabolic sensing in the hypothalamus and the regulation of physiologic processes. The convergence of molecular genetic techniques with intracellular signaling and neuroanatomical approaches in recent years has revealed mechanisms of hypothalamic regulation and physiology not previously possible utilizing any one of these methodologies alone. Building upon insights made possible by recent studies, the series examines the mechanisms by which hypothalamic centers sense the metabolic state and thereby regulate energy balance, glycemic control, reproduction, and other neuroendocrine and autonomic endpoints. Each of these reviews is written by a leader in this field of inquiry, in collaboration with up-and-coming young investigators.