Elevations in intracranial pressure often occur after traumatic brain injury. A limited array of medications is available for the treatment of intracranial hypertension. Metabolic suppression agents may be used in this situation to suppress electrical activity in the brain, diminish the cerebral metabolic rate of oxygen consumption, and, as a consequence, decrease cerebral blood volume and intracranial pressure. Propofol and pentobarbital have unique characteristics that make each desirable, yet difficult to use in the setting of traumatic brain injury. The subject of this review is to discuss the role of these agents in treating refractory elevated intracranial pressure through metabolic suppression.