The benefits of using hyperosmolar therapy to reduce intracranial hypertension have long been recognized in both human and veterinary medicine, with mannitol typically being the solute of choice. It is interesting to note that recent research in human medicine has favored the use of hypertonic saline in cases of brain injury. In this case report, administration of 3% saline reduced the acute neurologic signs observed in a 2.5-month-old Quarter Horse filly. This report will focus on the mechanisms, advantages, and disadvantages of using mannitol versus hypertonic saline to reduce cerebral edema.