Therapeutic hypothermia (whole body or selective head cooling) is becoming standard of care for brain injury in infants with perinatal hypoxic ischemic encephalopathy (HIE). Brain cooling reduces the rate of apoptosis and early necrosis, reduces cerebral metabolic rate and the release of nitric oxide and free radicals. Animal models of perinatal brain injury show histological and functional improvement due to of early hypothermia. The brain protection depends on the temperature and time delay between insult and beginning of treatment (more effective with cooling to 33 +/- 0.5 degrees C, and less than 6 hours after hypoxic-ischemic insult). Recent meta-analyses and systematic reviews in human neonates show reduction in mortality and long-term neurodevelopmental disability at 12-24 months of age, with more favourable effects in the less severe forms of HIE. The authors describe their experience in 53 term newborns with moderate-severe HIE treated with whole body cooling between 2001 and 2009, and studied with magnetic resonance imaging (MRI) and general movements (GMs) assessment. The creation of a network connecting the Neonatal Intensive Care Unit with the level I-II hospitals of the reference area, as part of regional network, is of paramount importance to enroll potential candidates and to start therapeutic hypothermia within optimal time window.