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The recent significant increase in research on depressive disorders in epilepsy has led to a greater recognition of its negative impact on multiple aspects of these patients' lives. Thus, a review of this topic could not be timelier.A population-based study suggests that a lifetime history of depressive disorders is relatively frequent in epilepsy patients. Contrary to long-held beliefs, the relation between these two disorders is bidirectional and a history of depression can often be identified before the first seizure has ever happened. Such a relation is the expression of common pathogenic mechanisms operant in both conditions, among which decreased binding of serotonin-1A receptors appears to be pivotal. Furthermore, a lifetime history of depression preceding the onset of epilepsy appears to be predictive of worse seizure control with pharmacotherapy and epilepsy surgery.These data are likely to change the way the relation between depression and epilepsy is conceptualized, to enhance the early recognition and treatment of this disorder and to generate further research on the impact of depressive disorders on seizure response to pharmacologic and surgical treatments.