This chapter focuses on long-term memory and its relationship to sleep with an emphasis on the role of sleep during memory consolidation. Declarative memory consolidation relies on the reactivation of the initially labile memory traces in the hippocampal formation as the temporary store, which drives memory reactivation in the cortex for long-term storage. Procedural memory of acquired skills is most often tested with regard to the effects of sleep. Regions critical for the consolidation of procedural memory are the cerebellum, striatum and motor cortex. Aside from pure memory consolidation, an added consideration for emotional memory is the effect of sleep on emotional salience. Long-term memory is dependent on the various sleep stages for consolidation. Aging is accompanied by general decline in memory and cognitive function. Many neurodegenerative diseases have profound deficits on systems critical for long-term memory consolidation and sleep regulation.