Current treatment guidelines for major depression recommend that a patient’s preference for psychotherapy or medication be considered in selecting the initial treatment approach. Researchers randomly assigned patients to 12 weeks of treatment with one of two antidepressant medications or with cognitive behavioral therapy (CBT). Patients’ preferences were only weakly associated with outcomes; preferences predicted treatment drop-out but not improvement. MRI scans identified that the degree of functional connectivity between an important emotion processing center (the subcallosal cingulate cortex) and three other areas of the brain was associated with the treatment outcomes. Specifically, patients with positive connectivity between the brain regions were significantly more likely to achieve remission with CBT, whereas patients with negative or absent connectivity were more likely to achieve remission with antidepressant medication.