Hypernatremia exerts its main effect on the brain through the osmotic gradient it creates on either side of the blood brain barrier, which is impermeable to sodium. This generates a transfer of water from the intracellular to the vascular sector leading to temporary cell shrinkage. Osmoregulation permits cerebral cells to accumulate osmoactive molecules in order to restore their initial volume. It has been demonstrated in animals with brain injury that intracellular dehydration occurs essentially in the nonlesioned hemisphere. In most experimental studies, the reduction in cerebral volume obtained by hypertonic saline (HS) perfusion is accompanied by an intracranial pressure decrease, even under hemorrhagic shock conditions. Initially, clinical studies successfully used HS, as an alternative to mannitol, in the treatment of acute and refractory intracranial hypertension. Then continuous infusion of HS, with the objective of inducing hypernatremia, had produced encouraging effects on intracranial pressure control. However, these results were limited to non-randomized studies, without control groups and mainly in pediatric patients. Nevertheless, the use of HS on intracranial hypertension, refractory to conventional treatments, could be reasonable under strict monitoring of natremia as well as its adverse effects.