There is strong evidence that prolonged, moderate cerebral hypothermia initiated within a few hours after severe hypoxia-ischemia and continued until resolution of the acute phase of delayed cell death can reduce neuronal loss and improve behavioral recovery in term infants and adults after cardiac arrest. This review examines the evidence that mild to moderate hypothermia is protective after hypoxia-ischemia in models of preterm brain injury and evaluates the potential risks. Induced hypothermia likely has potential to significantly reduce disability. Cautious, systematic trials are essential before hypothermia can be used in these vulnerable infants.