Rapidly growing experimental evidence supports the notion that sleep plays an active role in modulating synaptic plasticity in the brain and for stabilizing various types of memory. In addition, new technologies support the view of “off-line” reprocessing of recent experience during sleep. Conversely, recent analysis of the thalamocortical circuit establishes the reciprocal observation that sleep itself is a plastic process affected by waking experience. This overview synthesizes these convergent perspectives across a variety of brain regions and species, emphasizing neuronal activity in the visual cortex. We discuss possible strategies for approaching the interaction between sleep and plasticity utilizing the developing visual pathway as a reduced model.