The organizing goal of this research is to develop and evaluate a generalizable and economically feasible model for population-based management of major depression in primary care to reduce its population prevalence rate. Two inter-related studies will evaluate interventions to: (1) improve long-term adequacy of maintenance phase therapy; (2) prevent the transition from acute to chronic major depression; and (3) prevent relapse/recurrence among patients at high risk of relapse. Study 1: Evaluate whether Collaborative Care prevents the transition from acute to chronic major depression when depressed patients with a poor short-term outcome are targeted. A new randomized trial will evaluate the effectiveness of Collaborative Care provided to depressed patients with a poor short-term outcome. Collaborative Care consists of co-management of depressed patients by the primary care physician and a mental health specialist in the primary care clinic. Patients who have not experienced remission 6-8 weeks after initiation of antidepressant therapy will be randomly assigned to Collaborative Care or Usual Care (n=230). Outcomes will be assessed at 1, 3 and 6 months. Study 2: Evaluate whether a Relapse Prevention Program in primary care reduces relapse/recurrence rates when recovered patients at high risk of relapse are targeted. This randomized trial will evaluate a Relapse Prevention Program provided to primary care patients with a history of recurrent major depression who have remitted within 6-8 weeks of initiation of antidepressant therapy (n=380). The Relapse Prevention Program will incorporate shared decision-making about maintenance pharmacotherapy, patient training in symptom-monitoring, brief behavioral interventions, development of a written "Emergency Plan" for early response to relapse, and periodic telephone follow-up. Most high risk patients enrolled in the Relapse Prevention Program are expected to elect maintenance pharmacotherapy. Outcomes will be assessed 3, 6 ad 12 months after randomization.