Sleep responds to a variety of stressors, but the precise mechanisms whereby these alterations occur are not known. Ample evidence, however, testifies to corticotropin-releasing hormone (CRH) being uniquely situated to contribute to stressor-induced alterations in sleep. Behavioral responses to most stressors include periods of increased arousal and waking, regardless of whether the stressor is psychological in nature or results in physical insult. Furthermore, a large body of evidence suggests that CRH may also contribute to the regulation and maintenance of physiological waking. In this paper we hypothesize that CRH mediates waking, particularly after periods of exposure to acute stressors. The complex interactions of multiple systems determine the behavioral response to a particular stressor. As such, many factors determine the time course and duration of response, including stressor type, and the status of a particular system at the time of stressor presentation. We briefly review data indicating that CRH mediates physiological and behavioral responses to stressors, and present new data supporting the hypothesis that CRH may also be involved in the physiological regulation of waking.