Feeding behavior is tightly regulated by peptidergic transmission within the hypothalamus. Neuropeptide Y (NPY) is one of the most potent known stimulators of food intake and has robust effects on the hypothalamic feeding neuronal networks. A vast body of literature has documented the substantial effects of NPY on feeding behavior. However, the cellular mechanisms underlying the actions of NPY have only recently begun to be explored. The NPYergic signal, including its expression in hypothalamic neurons, its release into the synaptic space, and its direct or indirect receptor-mediated actions, is highly responsive to decreases in the metabolic state. The orexigenic NPY signal can suppress the anorexigenic drive to restore energy balance homeostasis when energy levels are low, such as after food deprivation. The NPY signal interacts with glucose- and fat-sensitive signals arriving in the hypothalamus and effects changes in anorexigenic pathways, such as those mediated by the melanocortins. Recent applications of electrophysiological methods to examine the neuronal activity and pathways engaged by NPY-mediated signaling have advanced our understanding of this orexigenic system. Furthermore, crucial roles for NPY pathways in the development of hypothalamic feeding circuitry have been identified by these means. Orexigenic NPY signaling is critical during development and its absence is lethal in adults, thus reflecting the essential role of NPY for the regulation of energy homeostasis.