Traumatic brain injury is the result of a primary, acute injury and is complicated by the development of secondary injury due to hypotension and hypoxia. Cerebral edema due to brain injury compromises the delivery of essential nutrients and alters normal intracranial pressure. The Monroe-Kellie Doctrine defines the principles of intracranial pressure homeostasis. Treatment for intracranial hypertension is aimed at reducing the volume of 1 of the 3 intracranial compartments, brain tissue, blood, and cerebrospinal fluid. Hyperosmolar therapy is one treatment intervention in the care of patients with severe head injury resulting in cerebral edema and intracranial hypertension. The effect of hyperosmolar solutions on brain tissue was first studied nearly 90 years ago. Since that time, mannitol has become the most widely used hyperosmolar solution to treat elevated intracranial pressure. Increasingly, hypertonic saline solutions are being used as an adjunct to mannitol in basic science research and clinical studies. Hyperosmolar solutions are effective in reducing elevated intracranial pressure through 2 distinct mechanisms: plasma expansion with a resultant decrease in blood hematocrit, reduced blood viscosity, and decreased cerebral blood volume; and the creation of an osmotic gradient that draws cerebral edema fluid from brain tissue into the circulation. The pediatric section of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies adapted previously published guidelines for the treatment of adult brain injury into guidelines for the treatment of children with traumatic brain injury. These guidelines offer recommendations for the management of children with severe head injury, including the use of mannitol and hypertonic saline to treat intracranial hypertension. Acute and critical care pediatric advanced practice nurses caring for children with severe head injury should be familiar with management guidelines and the use of hyperosmolar solutions. The purpose of this article is to assist the advanced practice nurse in understanding the role of hyperosmolar therapy in the treatment of pediatric traumatic brain injury and review current guidelines for the use of mannitol and hypertonic saline.