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To review the consequences of mechanical injury to the brain with an emphasis on factors that may explain the variability of outcomes and how this might be influenced.Information regarding the pathophysiology of traumatic brain damage contained in original scientific reports and in review articles published in recent years was reviewed from the perspective of a clinical neurosurgeon and a neuropathologist, each with major research interests in traumatic brain damage. The information was compiled on the basis of the knowledge of and personal selection of articles that were identified through selective literature searches and current awareness profiles. A systematic literature review was not conducted.Mechanical input affects neuronal and vascular elements and is translated into biological effects on the brain through a complex series of interacting cellular and molecular events. Whether these lead to permanent structural damage or to resolution and recovery is determined by the balance between processes that, on the one hand, mediate the effects of initial injury and subsequent secondary insults and, on the other, are manifestations of the brain's protective, reparative response. Experimental and clinical research has identified opportunities for altering the balance in a way that might promote recovery, but data demonstrating that this can lead to substantial clinical benefit are lacking. Recent evidence of genetically determined, individual susceptibility to the effects of injury may explain some of the puzzling variability in outcome after apparently similar insults and may also provide new opportunities for treatment.The understanding of traumatic brain damage that is being gained from recent research is widening and broadening perspectives from the traditional focus on mechanical, vascular, and metabolic effects to encompass wider, neurobiological issues, drawn from the fields of neurodevelopment, neuroplasticity, neurodegeneration, and neurogenetics. Neurotrauma is a fascinating area of neuroscience research, with promise for the translation of knowledge to improved clinical management and outcome.