Depression affects millions of people in the United States. Drugs used to treat depression can lead to weight gain, which could predispose a person to type 2 diabetes. Also, certain medications that may be used to treat depression with psychotic features can lead to metabolic syndrome and new-onset diabetes. Diabetes is another chronic health care condition that affects millions of people in the United States. Diabetes is the leading cause of nontraumatic amputations and a leading cause of blindness. Both conditions can result in a lower quality of life. Clinicians face challenges in treating either condition, but can face greater ones when the conditions occur together. This article reviews the literature concerning depression and diabetes.