Assessments of early response to antidepressant therapy based on condition severity have been contradictory due to the poor measurement properties of the instruments employed and the inappropriateness of condition severity as a criterion of improvement. It is argued that a more valid approach would involve the assessment of improvements in quality of life (QoL) associated with effective therapy. QoL instruments should reflect the views of the patients themselves, the only group able to comment authoritatively on whether they feel benefit from treatment. Research shows that it is the perceptions of the patients that determine whether treatment is sought, how far clinical advice is followed and whether treatment is discontinued. It is argued that the Quality of Life in Depression Scale is the only instrument available that has the required conceptual basis and psychometric properties to investigate the onset of response to antidepressant therapy.