Brain injury is the leading cause of death in our pediatric ICU [Au et al. Crit Care Med 36:A128, 2008]. Clinical care for brain injury remains largely supportive. Therapeutic hypothermia has been shown to be effective in improving neurological outcome after adult ventricular-arrhythmia-induced cardiac arrest and neonatal asphyxia, and is under investigation as a neuroprotectant after cardiac arrest and traumatic brain injury in children in our ICU and other centers. To induce hypothermia in children comatose after cardiac arrest we target 32-34 degrees C using cooling blankets and intravenous iced saline as primary methods for induction, for 24-72 h duration with vigilant re-warming. The objective of this article is to share our hypothermia protocol for cooling children with acute brain injury.