Epilepsy is a chronic disorder characterized by a spontaneous tendency to recurrent seizures which affects patients' cognitive, behavioral, psychological, and social functioning. Epileptic patients face various problems that result in a lower quality of life. Seizure frequency, drug side effects, psychological comorbidity, and stigma are the major factors affecting the quality of lives of patients with epilepsy. Depression, anxiety, psychosis, and cognitive impairment are some of the comorbid psychiatric problems accompanying the clinical picture in epilepsy. Also the role of antiepileptic drugs (AEDs) in psychopathology of epilepsy should not be underestimated. One of the most important reasons why health-related quality of life (HRQOL) has become important for epileptic patients is related with well-known characteristics of this disorder. Its chronic nature, presence of unexpected, intractable and frequent seizures, and stigma are some of these characteristics among others. With the review of the current literature, it can be concluded that there is still a need for further scientific research to find out more clear relation between epilepsy, comorbidities, and HRQOL.