The chronic and recurrent nature of major depressive disorder is receiving increasing attention.Approximately eight of ten people experiencing a major depressive episode will have at least one more episode during their lifetime, i.e. recurrent major depressive disorder.In the 1990s, prolonged or lifelong pharmacotherapy emerged as the main therapeutic tool for preventing relapses of depression. This therapeutic approach is based on the effectiveness of antidepressant drugs compared with placebo in decreasing relapse risk and on the improved tolerability profile of the newer antidepressants compared with their older counterparts. However, outcome after discontinuation of antidepressant therapy does not seem to be affected by the duration of administration. Loss of clinical effects, despite adequate compliance, has also emerged as a vexing clinical problem.The use of intermittent pharmacotherapy with follow-up visits is an alternative therapeutic option. This leaves patients with periods free of drugs and adverse effects and takes into account that a high proportion of patients would discontinue the antidepressant anyway. However, the problems of resistance (that a drug treatment may be associated with a diminished chance of response in subsequent treatments in those patients whose symptoms successfully responded to it but who discontinued it) and of discontinuation syndromes are substantial disadvantages of this therapeutic approach.In recent years, several controlled trials have suggested that sequential use of pharmacotherapy in the treatment of the acute depressive episode and psychotherapy in its residual phase may improve long-term outcome. Patients, however, need to be motivated for psychotherapy, and skilled therapists have to be available.Despite an impressive amount of research into the treatment of depression, there is still a paucity of studies addressing the specific problems that prevention of recurrent depression entails. It is important to discuss with the patient the various therapeutic options and to adapt strategies to the specific needs of patients.