Abstract The objective was to systematically review the medical literature and comprehensively summarize clinical research performed on biomarkers for pediatric traumatic brain injury (TBI) and to summarize the studies that have assessed serum biomarkers acutely in determining intracranial lesions on CT in children with TBI. The search strategy included a literature search of PubMed,(®) MEDLINE,(®) and the Cochrane Database from 1966 to August 2011, as well as a review of reference lists of identified studies. Search terms used included pediatrics, children, traumatic brain injury, and biomarkers. Any article with biomarkers of traumatic brain injury as a primary focus and containing a pediatric population was included. The search initially identified 167 articles. Of these, 49 met inclusion and exclusion criteria and were critically reviewed. The median sample size was 58 (interquartile range 31-101). The majority of the articles exclusively studied children (36, 74%), and 13 (26%) were studies that included both children and adults in different proportions. There were 99 different biomarkers measured in these 49 studies, and the five most frequently examined biomarkers were S100B (27 studies), neuron-specific enolase (NSE) (15 studies), interleukin (IL)-6 (7 studies), myelin basic protein (MBP) (6 studies), and IL-8 (6 studies). There were six studies that assessed the relationship between serum markers and CT lesions. Two studies found that NSE levels ≥15 ng/mL within 24 h of TBI was associated with intracranial lesions. Four studies using serum S100B were conflicting: two studies found no association with intracranial lesions and two studies found a weak association. The flurry of research in the area over the last decade is encouraging but is limited by small sample sizes, variable practices in sample collection, inconsistent biomarker-related data elements, and disparate outcome measures. Future studies of biomarkers for pediatric TBI will require rigorous and more uniform research methodology, common data elements, and consistent performance measures.