The raphe magnus is part of an interrelated region of medullary raphe and ventromedial reticular nuclei that project to all areas of the spinal gray. Activation of raphe and reticular neurons evokes modulatory effects in sensory, autonomic, and motor spinal processes. Two physiological types of nonserotonergic cells are observed in the medullary raphe and are thought to modulate spinal pain processing in opposing directions. Recent evidence suggests that these cells may modulate stimulus-evoked arousal or alerting rather than pain-evoked withdrawals. Nonserotonergic cells are also likely to modulate spinal autonomic and motor circuits involved in thermoregulation and sexual function. Medullary serotonergic cells have state-dependent discharge and are likely to contribute to the modulation of pain processing, thermoregulation, and sexual function in the spinal cord. The medullary raphe and ventromedial reticular region may set sensory, autonomic, and motor spinal circuits into configurations that are appropriate to the current behavioral state.