Objective This review discusses the experimental and clinical studies those show the expression of connexin 36 in the central nervous system and the possible role of connexin 36 in epileptic seizure. Data sources All articles used in this review were mainly searched from PubMed published in English from 1996 to 2012. Study selection Original articles and reviews were selected if they were related to the expression of connexin 36 in the central nervous system and its role in epilepsy. Results The distribution of connexin 36 is developmentally regulated, cell-specific and region-specific. Connexin 36 is involved in some neuronal functions and epileptic synchronization. Changes in the connexin 36 gene and protein were accompanied by seizures. Selective gap junction blockers have exerted anticonvulsant actions in a variety of experiments examined in both humans and experimental animals. Conclusions Connexin 36 plays an important role in both physiological and pathological conditions in the central nervous system. A better understanding of the role of connexin 36 in seizure activity may contribute to the development of new therapeutic approaches to treating epilepsy.