Worldwide, traumatic brain injury (TBI) is a major cause of mortality and morbidity with a substantial predicted increase in incidence. Despite an obvious need, there are no pharmacological treatment options for TBI because translation of neuroprotection from preclinical studies to clinical practice has so far failed. Here, we identify potential causes for this failure. We suggest that the monitoring and investigation tools that are commonly used in patients with TBI may provide an experimental medicine route to facilitate a more rational approach to translational research. This suggestion is underpinned by existing research data on disease biology, drug delivery, and treatment response obtained with these methods.