Hypoxic-ischemic encephalopathy causes significant morbidity and mortality in neonates. Preventing the secondary reperfusion injury that occurs following a hypoxic-ischemic event is paramount to ensuring the best possible neurologic outcome for the neonate. Induced hypothermia is currently being studied in various institutions as a means of neuroprotection for neonates at risk of severe brain injury following a hypoxic-ischemic event. This article highlights the pathophysiology of hypoxic-ischemic encephalopathy and the rationale behind the effectiveness of induced hypothermia. Nursing care and management of neonates being treated with induced hypothermia are discussed.