Over the past several decades, the neural mechanisms underlying REM sleep have become increasingly understood. A more detailed understanding of the respective roles of the pontine nuclei in the generation of REM sleep and its related phenomenon has allowed for the recognition of specific effects that brainstem lesions have on sleep. In humans, however, the effects of such lesions are limited to case reports and small case series. This article offers a comprehensive review of the basic neurobiology of REM sleep. In addition, we discuss specific clinical effects that various pontine lesions have with regard to REM sleep and the spectrum of clinical sleep disorders characterized by abnormalities in REM-related phenomena. We review the existing literature detailing the interactions between clinical sleep manifestations and brainstem pathology.