Traumatic brain injury (TBI) is one of the most complex diseases. Since the advent of imaging modalities, such as computed tomography (CT) and magnetic resonance imaging (MRI), there has been a quest to develop complementary diagnostic tools to provide more accurate assessment of injury severity and to improve outcome prediction. The progress has been slow. Because of this shortcoming, the treatment of TBI remains largely symptomatic and reactive rather than proactive.

The main obstacle in developing diagnostic, stratification and prognostic tools for TBI has been the heterogeneous nature of the disease. No two injuries are the same, and the pathology encountered ranges from diffuse injury, focal contusions and different types of haemorrhagic mass lesions to penetrating injuries. There are also differences in injury frequency, which can range from a single episode to multiple episodes as can occur in certain sporting events. Demographic and genetic variabilities, added with frequent concomitant injuries and treatment variability, increase this complexity.

TBI has lagged behind other medical and societal challenges in many ways. For instance, cardiovascular diseases can be diagnosed in a pathophysiologically meaningful way, and their treatment responsivity can usually be easily measured. In the case of TBI, the treatment is inherently dealing with the consequences of pathology once it has developed––instead of identifying patients in whom a pathological process will emerge and thus prevent it. The diagnostic tools to characterise TBI types and severity remain simplistic and rely largely on nonspecific symptoms that can be considered as snapshots that are unable to predict the disease evolution.

Blood-based biochemical markers (biomarkers) are promising tools to complement clinical variables and imaging findings in the diagnosis, monitoring and outcome prediction of patients who have sustained a TBI. In this chapter, the current evidence and clinical utility of biomarkers are reviewed and discussed.