Animal and human studies suggest that hypertonic saline is a potential therapeutic agent to assist with the medical treatment of patients with traumatic brain injury. It may have a place as osmotherapy to decrease brain size, predominantly of uninjured brain and has several potential advantages over mannitol. Hypertonic saline has clinically desirable physiological effects on cerebral blood flow, intracranial pressure and inflammatory responses in models of neurotrauma. Animal studies support its use, but definitive human trials using mortality end-points in brain trauma are lacking. Hypertonic saline may be considered a therapeutic adjunct to the medical management of traumatic brain injury, awaiting definitive evidence to support routine use.