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Traumatic brain injury (TBI) and cardiac arrest are important causes of morbidity and mortality in children. Improved diagnosis and outcome prognostication using validated biomarkers could allow clinicians to better tailor therapies for optimal efficacy.Contemporary investigation has yielded plentiful biomarker candidates of central nervous system (CNS) injury, including macromolecules, genetic, inflammatory, oxidative, and metabolic biomarkers. Biomarkers have yet to be validated and translated into bedside point-of-care or cost-effective and efficient laboratory tests. Validation testing should consider developmental status, injury mechanism, and time trajectory with patient-centered outcomes.Recent investigation of biomarkers of CNS injury may soon improve diagnosis, management, and prognostication in children with traumatic brain injury and cardiac arrest.