OBJECTIVE: Compliance with antidepressant medication is important in order to achieve all the goals of antidepressant therapy. These goals include symptom resolution, restoration of normal functioning and prevention of relapse or recurrent episodes. METHOD: We discuss compliance and review adverse symptoms that may occur when antidepressant treatment is abruptly discontinued or interrupted. RESULTS: The physician's role in managing compliance includes preventing or minimizing the risk for discontinuation symptoms, counselling patients regarding the risk for symptoms if doses are missed and choosing pharmacotherapy that is forgiving of non-compliance. Physicians also need to recognize the symptoms of discontinuation syndrome in order to differentiate patients who are non-compliant from patients who require a dosage adjustment or adjunctive therapy. Finally, physicians need to understand how to treat discontinuation symptoms when they do occur. CONCLUSION: Since published data indicate that between 30% and 60% of patients do not take their medications as prescribed, non-adherence to antidepressant medication is likely to be a significant clinical issue in the management of many patients.