Most patients with depression continue to have symptoms after treatment. It is well documented that these "residual" symptoms are common and are associated with increases in suboptimal long-term outcomes such as relapse and disability. While it is clear that residual symptoms, as a group, contribute to poor outcomes, individual residual symptoms have received relatively little attention. To some extent, this lack of attention reflects an uncertainty in the field about the relationship of the syndrome of depression to the symptoms by which the syndrome is defined.Recognizing that for clinicians and patients symptom relief is the goal of treatment, this article reviews the evidence that a symptomatic approach to individual residual symptoms is both feasible and useful. Evidence was gathered through a MEDLINE review of articles published in English from 1966 to 2002. Multiple keywords relating to symptoms, depression, and treatment were used.Many of the agents that psychiatrists use for augmentation of depression treatment, such as psychostimulants and alerting agents, atypical antipsychotics and mood stabilizers, and buspirone and benzodiazepines, have specific symptomatic effects, which raises the question of whether we are augmenting the core antidepressant effect or providing symptomatic relief. Fatigue, anxiety, sexual dysfunction, and sleep disturbances are all symptoms that are commonly leftover after treatment of depression. Some data indicate that treatment of these residual symptoms is efficacious and may affect the long-term outcome of depression.This discussion of the treatment of residual depressive symptoms raises a variety of research questions that should be addressed. Also implicit in this discussion are theoretical questions on the relationship between symptoms and syndrome.