Depression is a serious and frequent comorbidity of epilepsy and other neurological conditions. Here, we review recent studies on the relationship between epilepsy and depression with regard to diagnostic criteria, epidemiology, etiology and treatment. Depression in epilepsy can be described in the general framework of the diathesis-stress model: chronic stress exposure owing to the 'burden of epilepsy' and learned helplessness due to the threat of recurrent seizures as unpredictable aversive events represent psychological risk factors for the development of depression. Epilepsy-related factors (for example, focus site or side) have shown little effect on mood. Nonepileptic individuals who are adversely affected by seizures (for example, parents of pediatric patients with epilepsy, and patients with psychogenic nonepileptic seizures) show increased levels of depression, similar to patients with epilepsy. However, seizures, subclinical hypersynchronous neural discharges and some antiepileptic drugs may cause acute states of depressive mood or depression on a purely neurobiological basis. Antidepressant drugs and psychotherapy have shown moderate efficacy in the treatment of depression comorbidity, but randomized controlled trials in patients with epilepsy are lacking, especially for drugs.