Traumatic brain injury (TBI) results from physical damage to brain tissue that temporarily or permanently impairs brain function. The pathophysiology of TBI involves both primary and secondary injury cascades. The primary injury is caused directly by the mechanical force, while secondary injury involves complex biochemical and cellular processes such as ischemia, excitotoxicity, free radical formation, inflammation, and apoptosis. Specific pathophysiological features of TBI include reduced cerebral blood flow, cerebral vasospasm, metabolic dysfunction, excitotoxicity, oxidative stress, edema formation, and inflammation. A better understanding of the pathophysiology of TBI is important for developing new therapeutic strategies to improve outcomes.