This review synthesizes data from behavioral studies examining the role of sleep in memory storage with what is known about the molecular mechanisms of memory consolidation. There are striking similarities in the effects on memory storage of post-training pharmacological manipulations and post-training manipulations of sleep. For example, inhibition of protein synthesis is most effective if it occurs at a time post-training when rapid eye movement (REM) sleep is required for memory consolidation. The neurochemical changes that occur across sleep/wake states, especially the cholinergic changes that occur in the hippocampus during REM sleep, might provide a mechanism by which sleep modulates specific cellular signaling pathways involved in hippocampus-dependent memory storage.