Despite successful response to therapy, subsyndromal depressive symptoms appear to be the rule in unipolar depression. Residual symptoms are present in more than 30% of patients who respond to antidepressants, specifically in subjects with more severe initial illness. The most prevalent residual symptoms are affective, somatic, cognitive and sleep disturbance. It has been shown that such persistent symptoms are associated with a higher risk of relapse, chronicity and functional impairment; associated with neuroanatomical changes. It is important to consider the possibility of persistence subthreshold symptoms and look for new therapeutic strategies for improving the level of remission in the treatment of major depressive disorder.