Biological ill effects of oxidative injury from excess free radical production are implicated in many human conditions. Epilepsy is a chronic, dynamic neurological disorder associated with ongoing neuronal damage, particularly when uncontrolled. Oxidative injury may play a role in the initiation and progression of epilepsy, and therapies aimed at reducing oxidative stress may ameliorate tissue damage and favorably alter the clinical course. There is abundant in vivo evidence of oxidative injury in animal models of epilepsy and for efficacy of antioxidant therapy in reducing this injury in animal models of epileptogenesis. However, there is sparse direct clinical data on the use of antioxidants in human epilepsy. This review examines the evidence for the role of oxidative injury in epilepsy, the rationale for use of antioxidant therapy in epilepsy and appraises the current clinical performance of the studies of antioxidant therapies.