Acquired brain injury from traumatic brain injury, cardiac arrest (CA), stroke, and central nervous system infection is a leading cause of morbidity and mortality in the pediatric population and reason for admission to inpatient rehabilitation. Therapeutic hypothermia is the only intervention shown to have efficacy from bench to bedside in improving neurological outcome after birth asphyxia and adult arrhythmia-induced CA, thought to be due to its multiple mechanisms of action. Research to determine if therapeutic hypothermia should be applied to other causes of brain injury and how to best apply it is underway in children and adults. Changes in clinical practice in the hospitalized brain-injured child may have effects on rehabilitation referral practices, goals and strategies of therapies offered, and may increase the degree of complex medical problems seen in children referred to inpatient rehabilitation.