A brief description of the fundamental concepts of the biology and pathophysiology of excitatory amino acids, lactic acidosis, and free radicals in brain injury have been presented. For a comprehensive review of these topics, the references provide access to an extensive body of research in each of these areas. They represent a complex series of interrelated events that are set into motion at the initial injury. Some neurons are destined to die despite all therapeutic endeavors, but further investigation into the mechanisms responsible for delayed neuronal demise are in the early stages of human investigation or very close to clinical trials. Efforts directed at providing a favorable extracellular milieu for those neurons that are salvageable provide promise for continued improvements in outcome for patients with head injury.