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Considerable effort has led to an increased interest in emerging preclinical and clinical data regarding the pathophysiological changes in the posttraumatic brain. It is widely believed that delayed cell damage and death contributes to behavioral impairment following traumatic brain injury. However, no drug therapy to attenuate this process is available at present, and the development of new therapeutic regimen is urgently warranted. This manuscript represents a compendium of recent preclinical work undertaken to evaluate new pharmacologic strategies in the experimental setting as a first step towards the development of a therapeutic armamentarium directed to improve functional recovery in head-injured patients.