Barriers to patient adherence to antidepressant therapy include lack of knowledge in several important areas, including the nature of depression, the nature of treatments and how they can be expected to work, and the efficacy of pretreatment education. Other obstacles include unpleasant side effects of medications and negative attitudes and beliefs about medication on the part of patients and their families and treating physicians. Such barriers can be surmounted by approaches based on principles of good medical management, including: use of a multidisciplinary treatment team; education of patients and their families regarding the nature of depression and its treatments; the formation of an alliance among clinicians, patients, and family members; and the establishing of a clinic atmosphere that fosters such an alliance. Strategies to promote adherence should also address issues in practitioner disposition and training and barriers that arise as a result of the direct effects of depressive illness on the patient. In addition,such strategies must include measures appropriate to the different stages of depression treatment, including increased frequency of contact and intensity of support during acute treatment, regular monitoring during ongoing treatment, and the establishment of long-term relationships with those patients who have a history suggesting vulnerability to relapse.