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Residual symptoms occur in many depressive patients after acute treatment . There is growing evidence that residual symptoms are also prevalent in bipolar disorder during the euthymic phase and in unipolar depression, they are predictors of early relapse [2,3]. In long-term outcome, patients remitting from depression with residual symptoms, have more depressive symptoms and impaired social functioning, thus needing more aggressive treatment . Residual symptoms might be conceived as the persistence of the original mood disorder, despite in a milder presentation, or still be in relation to the neurobiological disorder substrate. Residual symptoms include core mood and functional symptoms of depression. The most common residual symptoms are sleep disturbances, fatigue, and disinterest. The clinician should be aware that patients despite being in apparent remission should be questioned thoroughly in order to identify residual cognitive difficulties, impairment of work and activities, psychic anxiety, sleep disturbances or mild depressive mood . The consequences of low-quality remission impairing psychosocial functioning have to be emphasized. In this presentation we will review the available evidence of the role played by the pharmacological treatments in the residual depressive symptoms.