Treatment of depression in patients with diabetes demands a multifaceted approach to both disease processes. Diabetes education, physical activity, and optimization of glycemic control are as integral to depression treatment as psychotherapy and pharmacotherapy. It is important to recognize late-life depression in diabetes as a chronic illness. Long-term maintenance pharmacotherapy is often required to achieve lasting remission. Response to therapy and reassessment for evidence of relapse or recurrence are essential as depression in diabetes tends to be resistant and prone to recurrence. Interventions that address acceptance of depression therapy are crucial to improving treatment of late-life depression in diabetes. Education of primary care physicians and the community are critical for recognition and optimal treatment of depression.