It is increasingly recognised that major depressive disorder can be a chronic condition with many patients experiencing recurrent episodes. Remission from a depressive episode implies the absence or near absence of depressive symptoms. However, for many patients the periods between depressive episodes are not symptom free. Residual symptoms are predictors of relapse or recurrence, and may be associated with residual psychosocial impairment. In clinical studies, remission is commonly defined using a cut-off score on a rating scale for depressive symptoms, such as a score of < or = 7 on the 17-item Hamilton scale. However, there is debate about which scales and cut-offs are optimal and full-length rating scales are not widely used in clinical practice. In spite of such issues, it seems clear that a therapy should aim at the most complete remission possible. Unfortunately, recent studies have highlighted that in clinical practice usually only a low rate of remission is achieved. Although long-term treatment with antidepressants can reduce the risk of relapse or recurrence only a minority of patients in clinical practice achieve this as treatment is often prematurely stopped due to long-term side effects such as sleep disturbance, sexual dysfunctioning and weight gain. Therefore, it represents an unmet need to come up with antidepressant drugs of greater efficacy and improved tolerability as such treatments could lead to more complete remission in more patients.