Hypoxic ischemic encephalopathy is a rare condition associated with high neonatal mortality and morbidity. Two randomized clinical trials have recently been published showing potentially promising results with hypothermia for neonatal encephalopathy. Additional clinical trials are underway to test cooling as a therapeutic modality for hypoxic ischemic encephalopathy. Outcome information about infants treated with hypothermia is available for children up to approximately 2 years of age. Longer-term outcome (ie, school age information) is currently lacking with respect to benefit and risk. Therapeutic hypothermia offers a potentially promising therapy for hypoxic ischemic encephalopathy. Hypothermia for encephalopathy should be considered an evolving therapy because of lack of long-term safety and efficacy data.