Diagnosing depression in the medically ill is a difficult diagnostic task for several reasons. Although sadness and depressed mood may be indicative of an underlying depressive syndrome, they may also be part of normal adaptation to a life-threatening disease.The somatic and vegetative symptoms included in diagnostic criteria are not specific and may in fact be attributable to hospitalization, treatments or medical illness. Treating depression is also difficult, because of concerns on drug-drug interactions and efficacy and safety of antidepressants in this group. In this Clinical Conference the authors answer questionson: which diagnoses canbemade in medical patients with depressive symptoms; prevalence of depression in different settings; comorbidity mechanisms (physiologicandbehavioral factors) that linkdepression to medical illnesses; and management of depression in this group.