Traumatic brain injury (TBI) is a major healthcare concern, constituting a major cause of death and disability throughout the world. Among the factors leading to TBI outcome are biochemical cascades which occur in response to primary and secondary injury. These mechanisms generate oxidative stress, an imbalance between oxidant and antioxidant agents that can result in neural dysfunction and death. After TBI, an assembly of oxidative stress markers (carbonylated proteins, lipid peroxides, reactive oxygen and reactive nitrogen species) are produced in the brain, while antioxidant defense enzymes decrease (GSH, ratio GSH/GSSG, GPx, GR, GST, G-6PD, SOD, CAT). This imbalance is directly related to the pathogenesis of TBI. Therefore, the development of antioxidant strategies is of primary interest in ongoing efforts to optimize brain injury treatment. The success of any drug intervention strategy relies, in part, on knowledge of the optimal dosage and therapeutic window for its administration. But while the enzymes involved in oxidative stress have been identified, the temporal course of this imbalance following TBI has yet to be determined. This would explain why most antioxidant strategies developed to treat patients with TBI have failed.