Posttraumatic seizures are relatively common following moderate to severe brain injury, although the mechanisms by which this occurs remain incompletely defined. A number of conventional antiepileptic drugs have proven effective in suppressing early seizures, defined as events occurring within the first 7days of injury. Early seizures may exacerbate intracranial hypertension and secondary tissue injury in the setting of trauma, and early seizure prophylaxis is an important component of the integrated management of patients with traumatic brain injury. However, suppression of early seizures does not reduce risk of late seizures, which may occur years after the initial event and are often associated with a lifetime burden of epilepsy. The study of molecular and cellular mechanisms associated with posttraumatic epileptogenesis and the development of validated animal models of late seizures are critical to reduce long-term epilepsy following brain trauma. To better study these disease-modifying therapies, future clinical trials should incorporate electrographic endpoints and prolonged patient follow-up.