- t he incidence of hypoxic ischemic encephalopathy in the United States is 2.8/1000 live births of which 10–15% of the infants succumb and 25–30% suffer permanent neurologic damage: mental retardation, cerebral palsy and epilepsy. The incidence is tenfold higher in the developing world [1-3]. Experimental evidence has confirmed that HIE is an evolving process lasting hours to weeks. Understanding the mechanisms that culminate in neuronal death has enabled the development of therapeutic strategies that limit the extent of the injury. Mild hypothermia is the most rigorously tested of these strategies and has been the subject of several recently published international multicenter randomized controlled trials. The results provide extensive information regarding the effectiveness and safety of this treatment in the management of the infants most at risk of significant brain injury. In this review, we present mechanisms of neuronal injury, the effect of hypothermia on these processes, and the results of the clinical trials. In addition, we present our experience with mild hypothermia in the treatment of moderate-severe HIE at Soroka Medical Center.