Epilepsy, in contradistinction to seizures, is a chronic disorder characterized by recurrent seizures. Pathophysiology of epilepsy involves alterations in voltage-dependent ion channels: reduction in inhibitory, i.e. GABA-mediated or increase in excitatory, i.e. glutamate-mediated inputs. Discovery of newer genetic models of epilepsy and use of models of injury-induced epilepsy based on electrically or chemically induced status epilepticus are recommended by NIH. In order to study the antiepileptic effect of drugs and discovering their mechanism of action, various in vitro and in vivo models of epilepsy have been devised which are discussed in the chapter.