Depressive symptoms frequently accompany physical illness, but the association between the two is complex. The combination has detrimental implications for the patient's health outcome, quality of life, medical treatment and health care use. The presence of physical symptoms of the medical illness can lead to challenges in recognising and diagnosing depression. This is best dealt with by placing greater emphasis on the psychological symptoms of depression. Recognition may be improved through use of appropriate screening tools for depression in medically ill patients. The management of depression in the setting of medical illness involves both general and specific approaches. General approaches include optimal treatment of the medical illness, exclusion of treatments that are associated with depressive symptoms, and simple general health strategies aimed at improving sleep and exercise. Good evidence exists for selective psychotherapeutic approaches and antidepressant treatments, but care is required to avoid drug-drug and illness-drug interactions with the latter.