Most studies on treatment methods in elderly depressive patients have included primarily patients in good physical health, excluding medical comorbidity, despite the fact that depression with medical comorbidity is the norm rather than the exception. In addition, depression is known to increase disability and mortality among the medically ill. This, therefore, becomes an extremely important issue. Although data are limited, the available evidence suggests that depression concomitant with medical illness can be treated. One or more of the selective serotonin reuptake inhibitors have demonstrated potential usefulness in depressed patients with ischemic heart disease, diabetes, dementia, and Parkinson's disease and in patients after stroke and after myocardial infarction. Large-scale trials are needed to assess not only the safety and effectiveness of agents for the treatment of depression in comorbid illness, but also the effects of depression on the course of the medical illness itself.