The goal of this article is to give an overview about the established current treatment concepts of traumatic brain injury, as well as an outlook on possible future developments in pharmacological neuroprotection. Modern medical treatment modalities of traumatic brain injury (TBI), including the preclinical management of severely head-injured patients, are reviewed. Since an increased intracranial pressure represents the most common complication of severe traumatic brain injury, frequently associated with the development of secondary brain damage, special emphasis was given to an updated treatment algorithm for this important condition. New insight into the pathophysiology of severe traumatic brain injury, especially the realization that brain damage develops sequentially, initiated several new treatment approaches aiming at the interruption of pathophysiological mechanisms leading to secondary brain injury. A high number of pharmacological substances have been tested for their ability to ameliorate secondary damage after TBI, or are currently under clinical trial. Although no drug has achieved this goal so far, the most promising of these therapeutical approaches, glutamate receptor antagonists, calcium channel antagonists, free radical scavengers, and cyclosporin A will be discussed in this review. Although a magical bullet for the treatment of traumatic brain injury has not been developed yet, several of the currently investigated neuroprotective strategies seem to be encouraging. A promising future approach might be to evaluate treatment strategies that combine several pharmacological agents, and possibly other treatment modalities, such as mild hypothermia, tailored according to the special pathology of patient subgroups, or even to every single patient in order to achieve an improvement in outcome after TBI.