Depression in epilepsy represents a frequently encountered psychiatric comorbidity that is likely to be related to a number of variables that are both biological and psychosocial. Current literature on the neurobiology of depression in epilepsy has focused on frontal lobe dysfunction. Modern studies of interictal psychiatric disorders of epilepsy have usually attempted to identify their similarities to the psychiatric disorders that meet current classificatory systems. In the interictal dysphoric disorder, eight key symptoms, grouped in three major categories, are identified: labile depressive symptoms, labile affective symptoms, and supposedly specific symptoms (paroxysmal irritability and euphoric moods). A specific instrument, named Interictal Dysphoric Disorder Inventory (IDDI), has been developed in the context of a collaborative German-Italian study. One of the most frequent methodological errors in studies of depression in epilepsy is the sole reliance on screening instruments for the diagnosis of depressive disorders.