The current standard of care in pediatrics is to administer hypotonic saline in maintenance parenteral fluids. The safety of this approach has never been evaluated. A review of the literature reveals that the administration of hypotonic fluids is potentially dangerous and may not be physiologic for the hospitalized child. There have been >50 reported cases of neurologic morbidity and mortality, including 26 deaths, in the past 10 years resulting from hospital-acquired hyponatremia in children who were receiving hypotonic parenteral fluids. Common childhood conditions requiring parenteral fluids, such as pulmonary and central nervous system infections, dehydration, and the postoperative state, are associated with a nonosmotic stimulus for antidiuretic hormone production, which can lead to free water retention and hyponatremia. Children are at particularly high risk of developing symptomatic hyponatremia as they have a larger brain-to-skull size ratio. The administration of isotonic saline in maintenance parenteral fluids is the most important prophylactic measure that can be taken to prevent the development of hyponatremia in children who receive parenteral fluids.