Publisher Summary This chapter focuses on the cellular and neurophysiological/neuropharmacological, with most of the emphasis on mechanisms relevant to rapid eye movement (REM) sleep. The chapter presents the sleep architecture and phylogeny/ontogeny so as to provide a basis for the later mechanistic discussions. The chapter discusses the REM sleep and the relevant anatomy and physiology, and describes the role of hypocretin/orexin in REM sleep control. Sleep may be divided into two phases. REM sleep is most often associated with vivid dreaming and a high level of brain activity. The other phase of sleep, called non-REM sleep or slow-wave sleep (SWS), is usually associated with reduced neuronal activity; thought content during this state in humans is, unlike dreams, usually nonvisual and consisting of ruminative thoughts. REM sleep in humans is defined by the presence of low-voltage fast EEG activity, suppression of muscle tone (usually measured in the chin muscles) and the presence of REMs. The REM sleep cycle length is 90 minutes in humans and the duration of each REM sleep episode after the first is approximately 30 minutes. While electroencephalography (EEG) staging of REM sleep in humans usually shows a fairly abrupt transition from non-REM to REM sleep, recording of neuronal activity in animals presents a quite a different picture. Neuronal activity begins to change long before the EEG signs of REM sleep are present.