In this chapter, we will review the recent developments relevant to understanding the neural systems that regulate REM sleep. We will review the initial discovery of REM sleep, followed by a brief description of the polysomnographic characterization of REM sleep. Our discussion will continue with a review of the principal brain-stem executive neurons responsible for REM generation. Pontine reticular formation neurons are involved in the expression of the majority of REM-sleep phenomena, including low-amplitude/high-frequency cortical EEG, the hippocampal theta rhythm, PGO waves/P-waves, and muscle atonia. Cholinergic brain-stem neurons are REM-on, promoting REM sleep; and serotonergic and noradrenergic brain-stem neurons are REM-off, suppressing REM sleep. GABAergic and glutamatergic mechanisms are also integral to REM sleep control. We will also survey the prominent nuclei of the midbrain and forebrain that promote, but do not generate, REM-sleep expression. The conclusion of this chapter will provide a review of three prominent models of REM-sleep regulation: the reciprocal-interaction model; the REM sleep “flip-flop” circuit model; and the revised model of paradoxical (REM) sleep control proposed by Luppi and colleagues.