Persisting severe brain edema causes intracranial hypertension and is associated with poor patient outcome. The treatment of acute intracranial hypertension is complex and multimodal. The most important options for medical treatment include controlled ventilation and osmotherapy, maintenance of brain and body homeostasis, and sedation. Osmotherapy is recommended in all relevant guidelines. The 2 osmotic agents most frequently used are mannitol and hypertonic saline. Both reduce intracranial pressure and improve cerebral perfusion and cerebral oxygen delivery. However, hypertonic saline seems advantageous over mannitol in many situations. In multitrauma patients, hypertonic saline contributes to hemodynamic stabilization and to the prevention of secondary insults. In addition, hypertonic saline has neurohumoral and immunologic effects, which may be beneficial in cerebral resuscitation.