Research into traumatic brain injury (TBI), focusing on changes in energy metabolism, cerebrovascular dysfunction, and brain parenchymal morphology, has not produced complete descriptions of mechanisms mediating the pathophysiology of TBI. New studies indicate that neurochemical alterations mediate important components of brain physiology associated with TBI, and these alterations may be responsive to pharmacologic therapy. We discuss rodent models of TBI, review current experimental evidence of muscarinic cholinergic and excitatory amino acid (EAA) receptor involvement in its pathophysiology, and address issues relevant to the interpretation of these data.