Our knowledge of cytokine sleep mechanisms has led to a view of brain organization of sleep positing that sleep is a local property of neural networks. Cortical columns oscillate between functional states; the sleeplike state of cortical columns is promoted by multiple cytokines. Cytokine-mediated sleep mechanisms support the hypothesis that sleep serves a synaptic-connectivity function and is tightly coupled to cerebral metabolism. Cytokine release from glia is enhanced by neuronal activity via adenosine triphosphate signaling and, in turn, these cytokines activate nuclear factor κ B, adenosine, and other downstream mechanisms thereby linking activity to local changes in state.