Through the use of newly developed experimental models of traumatic brain injury (TBI), researchers now recognize that much of the delayed neuronal damage that develops over hours to days following the initial injury may result from pathological alterations in the brain's endogenous neurochemistry. This dis regulation of central nervous system (CNS) homeostasis may lead to cell swelling, membrane disruption, cytoskeletal disorganization and proteolysis, alterations in brain metabolism and blood flow, and changes in neurotransmitter receptor physiology. The recent identification of many molecular and cellular responses to brain trauma has assisted in the development of rational targeted neuroprotective therapies. This column summarizes recent experimental advances in the development of therapeutic strategies and will provide an overview of the pharmacological compounds that are now being considered for, or used in, clinical trials for brain trauma.