The cerebrovascular and metabolic changes associated with traumatic injury to the CNS may be associated, in part, with pathologic alterations in endogenous neurochemical systems, including those involved with normal neurotransmission. These events may include alterations in neurotransmitter synthesis, release, or re-uptake mechanisms or changes in pre- or postsynaptic receptor activity. Other changes may include alterations in synthesis and release of endogenous neuroprotective compounds (e.g., antioxidants), the pathologic expression and release of endogenous "autodestructive" compounds, or regional changes in specific neurochemical factors known to be associated with inflammation (e.g., cytokines), or neuronal growth and regeneration (e.g., growth factors). Although the timing of the precise cascade of neurochemical events following CNS injury is poorly understood, recent identification of specific neurochemical alterations following traumatic brain injury provides an opportunity for the development and employment of therapeutic agents designed to modify gene expression, synthesis, release, receptor, or functional activity of these factors with subsequent attenuation of local secondary tissue damage. This article is a compendium of recent studies suggesting that modification of posttraumatic events with pharmacologic strategies can improve outcome and promote functional recovery in both animal models of traumatic CNS injury and in selected clinical trials.