Depression is more prevalent in patients with epilepsy than in the general population. The condition remains underdiagnosed because of underreporting of signs and symptoms. Another reason for lack of treatment is the belief that antidepressants have proconvulsant effects. Many antidepressants are known to lower the seizure threshold; however, data indicate that, at low doses, antidepressants possess anticonvulsant properties. Evidence also suggests that when an antidepressant is used within its therapeutic dosage range, the risk of seizure activity is low. When selecting an antidepressant for use in a patient with epilepsy, the clinician should carefully consider drug-drug interactions between antiepileptics and antidepressants. In general, selective serotonin reuptake inhibitors are considered first-line therapy. The efficacy of antidepressants in epilepsy patients may be enhanced with supportive therapy or psychotherapy.