Depression is a highly prevalent disorder at all levels of health-care delivery. Depression has an unfavourable effect on the prognosis of somatic illnesses, and is associated with excess mortality. Several mechanisms may contribute to these relationships. First of all, depression affects behaviour. Depressed patients show more unhealthy living habits, less compliance with medical treatment, and a higher number of accidents and suicides. Secondly, biological aspects of depression are important. Dysregulation of the neuro-immune system, hyperactivity of the hypothalamic pituitary adrenal axis, and autonomic dysregulation may all have a negative effect on both the prognosis of somatic illnesses and the lifespan. Although studies have suggested beneficial effects of the treatment of depression in (somatic) patients, it remains unclear whether treatment may also affect survival. Further research is needed to investigate the occurrence of and to unravel the mutual influences of depression and somatic illnesses, to search for possible pathogenetic mechanisms that may underlie both depression and medical disorders, and to assess the effects of depression treatment on biological parameters and survival.