The majority of patients with epilepsy suffer from one or more psychiatric or somatic comorbid conditions, whose nature and prevalence vary with age and sociodemographic factors. In these patients, comorbid conditions have a major adverse effect on overall health and quality of life and substantially increase health care costs. Although there is an understanding of epidemiological aspects of the comorbidity of epilepsy, little is known about causal relationships, clinical interventions to prevent comorbidities, or the management of patients with multiple coexisting conditions. Both the effects of epilepsy therapies on comorbidities and the effects of comorbidities on the efficacy of epilepsy treatments warrant further study.