Hypoxic-ischemic encephalopathy (HIE) is a major cause of morbidity and mortality in neonates. Hypoxic-ischemic encephalopathy occurs as a result of a perinatal hypoxic-ischemic event just prior to or during delivery. Therapeutic hypothermia using whole body cooling is the current treatment of choice to reduce brain injury and improve long-term neurodevelopmental outcomes for neonates with HIE. All English language articles published since 2005 in PubMed and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) were analyzed for existing evidence-based methods for whole body cooling. Whole body cooling is effective in the treatment of HIE in term and near-term neonates. Further research is needed to investigate the use of adjunctive therapies in conjunction with whole body cooling for improved neuroprotection.