The current dogma is: “There is no treatment for traumatic brain injury (TBI)”. The statement is both true and false. True, there is no treatment for TBI per se, because TBI is an EVENT, like infection, it initiates complex pathobiological responses. The statement is also false, because there is, at least, a dozen plus molecules that can efficiently treat TBI-INDUCED conditions. So why has the development of efficient pharmacotherapies to improve outcomes in humans been so challenging? There are several reasons for the 100% failure rate in clinical trials (Agoston, 2021). The most common identifiable cause is the failure to identify the TBI-induced pathobiological changes, i.e. the disease endophenotypes. Without knowing the disease endophenotype, it is impossible to identify the molecular targets for pharmacological intervention. Another equally important cause of the current failure is the inability to identify the onset and temporal pattern of TBI-induced pathobiological change(s). Without such information, the therapeutic window for targeted pharmacological intervention cannot be identified. In addition to these fundamental errors, most studies are using clinically irrelevant animal modeling, resulting in low level of translatability.