Cerebral edema is a significant cause of elevated intracranial pressure and a consequence of secondary injury following traumatic brain injury. The use of hyperosmolar agents has been theorized to reduce intracranial pressure through osmotic effects on the water content of the injured brain. The most commonly used agents for this purpose are mannitol and hypertonic saline. While these agents have demonstrated efficacy, prospective, randomized clinical data are somewhat limited. This article reviews the available data concerning the safety, efficacy, and monitoring of osmotic agents when used to treat elevated intracranial pressure.