The arousal system involves multiple distributed neural networks working in harmony to permit normal sleep-wake cycles, satisfy internal drive states, and respond to environmental demands. Disorders of arousal involve pathology of the brainstem, thalamus, or widespread areas of both cerebral hemispheres. A parallel series of distinct neural networks using dopamine, histamine, serotonin, acetylcholine, and norepinephrine as neurotransmitters originates in the brainstem. Brain death represents the most severe disturbance of arousal, with total and irreversible cessation of any brain function. Coma is the state of neurological unconsciousness exhibited by unarousable unawareness of the external environment that is due to extensive damage to or depressed function of both cerebral hemispheres, bilateral diencephalic structures, or the ascending reticular activating system. A specific rehabilitative strategy is coma stimulation, in which structured sensory stimulation is administered for the purposes of improving sensory awareness and facilitating improvements in arousal and awareness.