There is no single treatment for any complex medical condition, and yet, the quest for a neuroprotective magic bullet for TBI has been the holy grail of neurotrauma research for many decades. Recent advances have increasingly informed a better understanding the complex biological processes underlying TBI across injury types, severities and time post-injury. Identification and validation of objective biological markers can improve future TBI classification, prognosis and intervention, and is now bringing into view a whole new horizon of precision, individualized, mechanism-based therapeutics.