Injuries to the central nervous system continue to be vast contributors to morbidity and mortality; specifically, traumatic brain injury (TBI) is the most common cause of death during the first four decades of life. Several modalities are used to monitor patients suffering from TBI in order to prevent detrimental secondary injuries. The microdialysis (MD) technique, introduced during the 1990s, presents the treating physician with a robust monitoring tool for brain chemistry in addition to conventional intracranial pressure monitoring. Nevertheless, some limitations remain, such as limited spatial resolution. Moreover, while there have been several attempts to develop new potential pharmacological therapies in TBI, there are currently no available drugs which have shown clinical efficacy that targets the underlying pathophysiology, despite various trials investigating a plethora of pharmaceuticals. Specifically in the brain, MD is able to demonstrate penetration of the drug through the blood-brain barrier into the brain extracellular space at potential site of action. In addition, the downstream effects of drug action can be monitored directly. In the future, clinical MD, together with other monitoring modalities, can identify specific pathological substrates which require tailored treatment strategies for patients suffering from TBI.