TBI (traumatic brain injury) is a major cause of death among youth in industrialized societies. Brain damage following traumatic injury is a result of direct and indirect mechanisms; indirect or secondary injury involves the initiation of an acute inflammatory response, including the breakdown of the blood-brain barrier (BBB), brain edema, infiltration of peripheral blood cells, and activation of resident immunocompetent cells, as well as the release of numerous immune mediators such as interleukins and chemotactic factors. TBI can cause changes in molecular signaling and cellular functions and structures, in addition to tissue damage, such as hemorrhage, diffuse axonal damages, and contusions. TBI typically disturbs brain functions such as executive actions, cognitive grade, attention, memory data processing, and language abilities. Animal models have been developed to reproduce the different features of human TBI, better understand its pathophysiology, and discover potential new treatments. For many years, the first approach to manage TBI has been treatment of the injured tissue with interventions designed to reduce the complex secondary-injury cascade. Several studies in the literature have stressed the importance of more closely examining injuries, including endothelial, microglia, astroglia, oligodendroglia, and precursor cells. Significant effort has been invested in developing neuroprotective agents. The aim of this work is to review TBI pathophysiology and existing and potential new therapeutic strategies in the management of inflammatory events and behavioral deficits associated with TBI.