Mannitol has long been the “gold standard” for treatment of cerebral edema and refractory intracranial hypertension in traumatic brain injury, subarachnoid hemorrhage, and stroke. Studies performed in animals have shown that hypertonic saline (HS), in doses ranging from 3% to 10%, may be more effective than mannitol in treating these populations. Recently, randomized clinical trials have evaluated the efficacy and safety of HS versus mannitol in the treatment of elevated intracranial pressure (ICP). This research has been prompted by mounting concern about the side effects of mannitol, the limited ability to give multiple doses of the drug, and an increased understanding of cerebral physiology. Four studies have compared the use of HS and mannitol in brain-injured populations. These studies have shown that not only is HS a safe drug (no patients experienced adverse effects), it is also more efficient in reducing ICP. Efficiency is defined as the drug's ability to decrease ICP to acceptable levels and to maintain lower ICPs for a longer duration of time. It is important for nurses who administer osmotic diuretics to evaluate and understand the current research to provide educated and appropriate care.