Neonatal Hypoxic-ischemic encephalopathy in full term infants has been associated with a high risk for morbidity and mortality. The patho-physiology of brain injury following hypoxia-ischemia, noted in preclinical models, is a cascade of events resulting from excitotoxic and oxidative injury culminating in cell death. Hypothermia has been noted to be protective by inhibiting various events in the cascade of injury. Major randomized clinical trials in neonatal HIE have demonstrated reduction in death and disability and continued safety and efficacy of neuroprotection in childhood. There is now clinical and imaging evidence for hypothermia as neuroprotection. Hypothermia should be offered to term infants with either severe acidosis at birth or resuscitation needing continued ventilation and evidence of either moderate or severe encephalopathy within 6 hours of birth. The target temperature should be 33° to 34 °C and duration of cooling should be 72 hours, as per the published trials. Rewarming should be slow, at 0.5 °C per hour. Infants should have serial neurological examinations during and at the end of cooling and at discharge. Multiorgan function should be supported and hypocarbia should be avoided during ventilator therapy. If available, the amplitude integrated EEG should be obtained prior to cooling and following rewarming. All infants should have magnetic resonance brain imaging studies within 1 to 2 weeks of age. Information from the neurological examination, aEEG and MRI studies will be helpful in discussing prognosis with parents. All infants should be followed for a minimum of 18 months to evaluate growth parameters and neurodevelopment al outcome.