Studies in encephalopathic infants have demonstrated a brief phase of normal cerebral energetics following hypoxia-ischaemia prior to development of delayed energy failure. In experimental models, mild hypothermia has shown a consistent neuroprotective action, although its efficacy is critically dependent on the severity of the primary insult, the delay in initiating cooling, and the duration and depth of hypothermia. Early electroencephalographic assessment of encephalopathic infants has the potential to provide objective information about the preceding insult, aiding the selection of infants for enrollment to clinical trials. Preliminary results from a large randomised trial of selective head cooling suggest that early intervention can lead to significantly improved outcome in a subgroup of encephalopathic infants with intermediate electroencephalographic abnormalities. Further research in established experimental models is essential to improve the identification of suitable infants for treatment, to investigate the importance of variations in regional brain temperature, and to examine the therapeutic potential of hypothermia combined with other neuroprotective agents.