Depression has a major impact on quality of life in patients with epilepsy and is also the main risk factor for the increased suicide rate in epilepsy. The frequency of depressive disorders depends on the severity of epilepsy and the localization of the epileptogenic focus, with a prevalence of <or=50% in patients with intractable temporal lobe epilepsy. The diagnosis of depression in epilepsy may be difficult because symptoms of depression may be fluctuating, and some symptoms, such as memory complaints, may be misinterpreted as being a consequence of drug treatment or the epilepsy per se. Affective disorders in epilepsy may differ from those seen in patients without epilepsy. A possibility exists that patients with epilepsy will develop a specific interictal dysphoric syndrome related to limbic system dysfunction. Recent epidemiologic studies suggest a bidirectional relation between depression and epilepsy. Depression does not necessarily occur after the onset of epilepsy; the sequence may as well be the other way round, suggesting a common underlying mechanism for both disorders. Classic bipolar disorder type I is rarely seen in epilepsy, and manic episodes occur almost exclusively in the setting of postictal psychosis or after epilepsy surgery. This article explores the clinical manifestations of depressive and manic disorders in epilepsy and the differences from bipolar disorder.