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The possibility that hypothermia has a therapeutic role during or after resuscitation from severe perinatal asphyxia has been a longstanding focus of research. Early studies using short periods of cooling had limited and contradictory results. We now know that resuscitation can be followed by a “latent” phase, characterized by transient recovery of cerebral energy metabolism, before secondary deterioration occurs with seizures, cytotoxic edema, and cerebral energy failure 6 to 15 hours after birth. Recent experimental studies have shown that moderate cerebral hypothermia initiated as soon as possible in the latent phase, before the onset of secondary injury, and continued for 48 hours or more is associated with potent, long-lasting neuroprotection. These encouraging results must be balanced against the well-known adverse systemic effects of hypothermia. Randomized clinical trials are in progress to test the safety and efficacy of cerebral hypothermia.