Epilepsy is a common neurological disease characterized by recurrent seizures. About 70 million people were affected by epilepsy or epileptic seizures. Epilepsy is a complicated complex or symptomatic syndromes induced by structural, functional, and genetic causes. Meanwhile, several comorbidities are accompanied by epileptic seizures. Cognitive dysfunction is a long-standing complication associated with epileptic seizures, which severely impairs quality of life. Although the definitive pathogenic mechanisms underlying epilepsy-related cognitive dysfunction remain unclear, accumulating evidence indicates that multiple risk factors are probably involved in the development and progression of cognitive dysfunction in patients with epilepsy. These factors include the underlying etiology, recurrent seizures or status epilepticus, structural damage that induced secondary epilepsy, genetic variants, and molecular alterations. In this review, we summarize several theories that may explain the genetic and molecular basis of epilepsy-related cognitive dysfunction. (C) 2019 Elsevier Inc. All rights reserved.