Any chronic disease is associated with an increased prevalence of mood disorders and depression. Diabetes is unique in that it places the burdens of invasive blood glucose monitoring, regimentation of diet and exercise, and often multiple daily insulin injections into the hands of the individual. Therefore, it is not surprising that depression may be three times more prevalent in the diabetic population when compared with nondiabetic individuals. Depressed patients with diabetes have been shown to have poorer glycemic control and a higher incidence of microvascular and macrovascular complications. Treatment of the depression associated with diabetes with either pharmacologic therapy or behavioral intervention has been shown to result in improved glycemic control and quality of life. Specific side effects of commonly used antidepressant medications, which have particular bearing on the diabetic state, are discussed. Future research into the causal relationship of depression to the onset on diabetes, longitudinal studies looking at depression and the rate of occurrence of diabetic complications, and the impact of the early development of healthy coping mechanisms and the treatment of depression on the natural history of diabetes are needed.