Developmentally regulated changes in the immature brain may contribute to an age-related period of susceptibility to seizures and brain injury resulting from impaired brain perfusion. It is therefore crucial that immature animal models be developed that are relevant to ischemic injury in the immature brain as an important cause of neurologic morbidity. We review here the animal models for ischemic injury in the immature brain with a focus on rodent models. These models have begun to be used for neuroprotective studies. Of the findings from these pre-clinical studies, a few interventions, including hypothermia and magnesium, have been studied in clinical trials. The published results so far from these clinical studies are reviewed here as well. More pre-clinical and clinical studies are needed to assess approaches to preventing ischemic brain injury in term neonates, infants, and children.