Depressive disorders are the most frequent psychiatric disturbances associated with epilepsy in adolescents and include a broad and heterogeneous spectrum of conditions that share hallmark features and symptoms such as sadness, irritability, decreased motivation or interests, fatigue, withdrawal, hopelessness, anhedonia, changes in appetite and weight, and sleep disturbances that are persistent and pervasive most days for at least 2 weeks. Using generic self-report depression surveys and current diagnostic codes, clinical and surveillance studies have revealed prevalence rates of 20–25% for depression in youth with epilepsy, with adolescents showing particular vulnerability. Furthermore, 20% of youth with epilepsy endorse suicidal ideation, and youth endorsing suicidal ideation do not necessarily have clinical symptoms of depression. Considering that depression in youth with epilepsy is a common comorbidity, characterized by poorer psychosocial and healthy-related outcomes and increased risk of suicide, a brief, free measure of specific depressive symptoms in youth with epilepsy would be beneficial. Recently, the NDDI-E-.Y inventory has been developed from the adult NDDI-E, and validated in many countries. NDDI-E-Y showed reliable and construct validity, being a brief screening tool (12 items) that can be easily included in routine epilepsy care.For the management of depressive symptoms in adolescents, interventions can be distinguished in non-pharmacological and pharmacological. The first includes psychoeducation which should clarify to adolescents and parents the main features of epileptic disorder, side effects of antiepileptic drugs, treatment modalities, how to cope with learning and social difficulties, in order to improve quality of life. Concurrently, a cognitive-behavioral therapy (CBT) including individual therapy, supportive and family therapy and school services, should be carried on. Psychopharmacology for depressive symptoms should be deserved to moderate to severe depressive symptomatology, only after deep assessment of prior and current antiepileptic and/or psychopharmacologic treatment. SSRIs including fluoxetin, sertraline, fluvoxamine and escitalopram should be first considered. Data coming from experimental studies in animals and humans seem to confirm no decrease of seizure threshold by SSRI adjunctive therapy.