Traumatic Brain Injury (TBI) is described as the brain damage occured by direct and indirect forces. Although TBI is a common health care problem, its diagnosis, management and the prediction of prognosis still remain obscure.S100B, neuron specific enolase (NSE), Glial fibrillary acidic protein (GFAP), Myelin-basic protein (MBP) and cleaved tau protein (CTP) have been evaluated in the diagnosis and prediction of prognosis in moderate-major TBI.S100B is the most investigated brain injury marker. Post-traumatic S100B levels correlate with the intracranial injury presence evaluated by computed tomography, also high S100B levels seem to predict low Glasgow Coma Scale (GCS) scores.GFAP is basic interval filament proteins of astrocytes. Measurement of circulatory GFAP is an important tool in the diagnosis of astrogliosis.MBP connects myelin sheaths to oligodendrocytes. It is the basic protein of myelin sheath. Excessive posttranslational modification of MBP occurs in both normal development of central nervous system and multiple sclerosis.Cerebrospinal fluid and serum NSE levels can be used in the diagnosis of benign and malign central nervous system diseases.Tau, found in neuronal axons, is a protein related with microtubules. It covers the axonal microtubules and stables them. The phosphorylation of TAU through serine and threonine kinases regulate its, both the normal and the pathological functions.Beneficial effects of biomarkers in clinical decisions will increase if obstacles like, determination of cut-off levels, extensive use and price and accurate measurement techniques, are overcome.