Results of experiments performed in animal epilepsy models and human epilepsy during the past decade indicate that the epileptic brain is not a stable neuronal network, but undergoes modifications caused by the underlying etiology and/or recurrent seizures. In many forms of epilepsy, such as temporal lobe epilepsy, the underlying etiologic factor triggers a cascade of events (epileptogenesis) leading to spontaneous seizures and cognitive decline. In some patients, the condition progresses, due in part to recurrent seizures. The current treatment of epilepsy focuses exclusively on preventing or suppressing seizures, which are symptoms of the underlying disease. Now, however, we are beginning to understand the underlying neurobiology of the epileptic process, as well as factors that might predict the risk of progression in individual patients. Thus, there are new opportunities to develop neuroprotective and antiepileptogenic treatments for patients who, if untreated, would develop drug-refractory epilepsy associated with cognitive decline. These treatments might improve the long-term outcome and quality-of-life of patients with epilepsy. Here we review the available data regarding the neuroprotective effects of antiepileptic drugs (AEDs) at different phases of the epileptic process. Analysis of published data suggests that initial-insult modification and prevention of the progression of seizure-induced damage are candidate indications for treatment with AEDs. An understanding of the molecular mechanisms underlying the progression of epileptic process will eventually show what role AEDs have in the neuroprotective and antiepileptogenic treatment regimen.