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The rapid progress in biomarker science is on the threshold of significantly changing clinical care for infants in the neonatal ICU. Infants with neonatal brain injuries will likely be the first group whose management is dramatically altered with point-of-care, rapidly available brain biomarker analysis. Providing an interim update on progress in this area is the purpose of this review.Highlighted findings from the past 18 months of publications on biomarkers in neonatal brain injury include; Specific nonbrain markers of cardiac health and global asphyxia continue to provide information on brain injury after hypoxic–ischemic encephalopathy (HIE). Prediction of injury in the piglet hypoxia-ischemia model is improved with the use of a combination score of plasma metabolites. In a neonatal piglet model of perinatal hypoxia–ischemia, a systemic proinflammatory surge of cytokines has been identified after rewarming from therapeutic hypothermia. New biomarkers identified recently include osteopontin, activin A, neutrophil gelatinase-associated lipocalin, secretoneurin, Tau and neurofilament light protein. Brain-based biomarkers differ in their ability to predict short-term in-hospital outcomes and long-term neurologic deficits.Neonatal brain biomarker research is currently in its very early development with major advances still to be made.