 This study is a randomized, controlled trial of Mindfulness-Based Cognitive Therapy MBCT versus Health-Enhancement Program HEP for patients with treatment-resistant major depressive disorder MDD. Both arms of the study will continue to receive the standard medication management treatment as usual TAU throughout the study. MBCT is a new technique that has been found to be effective for prevention of relapse in individuals in complete recovery from depression. MBCT is a group-based, 8-week intervention that uses mindfulness meditation as its core therapeutic ingredient. It teaches people to have a different relationship to depressive thoughts and feelings. This study will use an active condition called the Health Enhancement Program HEP which was specifically developed to serve as a comparison condition for mindfulness interventions. HEP has been shown to decrease global stress levels and to increase perceived health. Stress has been considered a contributor to depression. One hundred and seventy four patients with MDD who have failed two or more adequate antidepressant trials will be identified and randomly assigned to one of two groups: MBCTTAU or HEPTAU. All patients who enroll in the study will undergo follow-up assessments at 3, 6, 9 and 12 months following the intervention. A supplemental portion of the study will enroll 88 patients to undergo functional magnetic resonance imagining fMRI scans immediately before and after treatment to better understand the neural pathways implicated in depression and those that may be affected through treatment. 