The current diagnostic criteria for traumatic brain injury (TBI) are heavily reliant on an accurate clinical history of events. Diagnosis of mild injury relies on one or more of the following: confusion or disorientation, loss of consciousness (LOC) for 30 min or less, post-ictus amnesia for less than 24 h and/or other transient neurological abnormalities and a Glasgow Coma Score (GCS). Given the nature of the condition it is obvious that significant clinical challenges remain to identify in the cases of mild TBI, and additionally to grade more severe forms so that appropriate treatment is received. The lack of clinically useful biomarkers in the serum of TBI patients is a significant barrier to improving their outlook. Discovery of such markers would aid the timely diagnosis of novel and recurrent disease in a minimally invasive manner. A PubMed search was performed to identify studies reporting serum biomarkers in traumatic brain injury. Details regarding the biomarkers analysed, specificity, indications for outcome and statistical significance were recorded. A total of 40 manuscripts reporting 11 biomarkers were identified in the literature. All but a few studies reported statistically significant differences in biomarker expression between groups. We conclude that serum biomarkers of TBI are an effective means for investigating the condition. However, the lack of novel markers identified in this mass of studies highlights the need to adopt new measure of biomarker identification.