Depression is the most frequent comorbid psychiatric disorder in epilepsy. The occurrence of symptoms of depression in epileptic patients is the expression of multiple pathogenic mechanisms: the neurochemical and neurophysiologic changes that take place in limbic structures in the course of the epileptic disorder, an iatrogenic process (negative psychotropic properties of antiepileptic drugs, epilepsy surgery), a reactive process to a chronic disorder and genetic risk factors. Depression prevalence in patients with epilepsy has been estimated at between 9 and 62%. The literature remains inconclusive regarding risk factors of depressive disorders in epilepsy. Data concerning the role of demographic, genetic, iatrogenic variables, clinical characteristics of epilepsy and its treatment, comorbidity are ambiguous. Comorbid depression in epilepsy affects negatively the health-related quality of life, increases suicide risk and costs of medical care when compared to patients without depression Selective serotonin reuptake inhibitors and selective serotonin and norepinephrine reuptake inhibitor are first-line treatment of depression in patients with epilepsy.