BACKGROUND: Psychotherapy is the principal nonpharmacologic method for the management of depression, but its usefulness for depressed patients with diabetes remains unknown. OBJECTIVE: To assess the efficacy of cognitive behavior therapy (CBT) for depression in patients with diabetes. DESIGN: Randomized, controlled trial. SETTING: Referral-based academic medical center. PATIENTS: 51 patients with type 2 diabetes and major depression. INTERVENTION: Patients were assigned either to a group that received 10 weeks of individual CBT or to a control group that received no specific antidepressant treatment. All patients participated in a diabetes education program to control for the effects of supportive attention and the possible influence of enhanced diabetes control on mood. MEASUREMENTS: Degree of depression was measured by using the Beck Depression Inventory; glycemic control was measured by using glycosylated hemoglobin levels. Outcomes were assessed immediately after treatment and 6 months after treatment. RESULTS: The percentage of patients achieving remission of depression (Beck Depression Inventory score < or = 9) was greater in the CBT group than in the control group: posttreatment, 85.0% of patients in the CBT group (17 of 20) compared with 27.3% of controls (6 of 22) achieved remission (difference, 57.7 percentage points [95% CI, 33 to 82 percentage points]) (P < 0.001); at follow-up, 70.0% of patients in the CBT group (14 of 20) compared with 33.3% of controls (7 of 21) achieved remission (difference, 36.7 percentage points [CI, 9 to 65 percentage points]) (P = 0.03). Post-treatment glycosylated hemoglobin levels were not different in the two groups, but follow-up mean glycosylated hemoglobin levels were significantly better in the CBT group than in the control group (9.5% compared with 10.9%; P = 0.03). CONCLUSIONS: The combination of CBT and supportive diabetes education is an effective nonpharmacologic treatment for major depression in patients with type 2 diabetes. It may also be associated with improved glycemic control.