Major depressive disorder is difficult to treat due to its chronic and recurrent nature and the poor performance of most pharmacologic treatment options. To improve patient outcomes, clinicians should become familiar with moderators of antidepressant response, implement measurement-based care, and follow treatment algorithms. The use of electronic medical records and computerized decision support systems may improve documentation and facilitate clinicians' adherence to current standards of care. This Performance Improvement activity focuses on improving treatment outcomes for antidepressant therapy through familiarity with moderators of antidepressant response and the use of treatment algorithms, measurement-based care, and electronic medical records. © Copyright 2011 Physicians Postgraduate Press, Inc.