Brain-specific biomolecules are being increasingly investigated as a viable alternative to the clinical scores and radiological features, on which we still rely upon for stratification, therapy and predicting outcome in traumatic brain injury (TBI). TBI generally leads to release of various chemical compound within the cerebrospinal fluid (CSF) or blood depending on the severity of injury, which were studied variedly in last decades. However, most of these compounds being non-specific to brain, their applicability was challenged further. This review encompasses the novel and promising biomarkers being studied in the present decade, with encouraging results in laboratory and animal or human models. © 2018