Loss and bereavement can be regarded as risk factors for the development of psychiatric and medical illness. Vulnerability to physical illness and mortality are increased during the first 2 years of bereavement, with men at higher risk than women. Symptoms of anxiety and a frank depressive syndrome are common during the first months of bereavement and, although depressive symptoms are usually transient and self-limited, bereaved individuals not rarely go on to develop major depression. In our perspective, loss perceived as irreparable, and persistence of perceived loss may favour the development of complicated grief and depression. Factors such as unexpectedness, absence of social support, concurrent loss or illness, and grief proneness may predict poor adjustment after bereavement. Complicated bereavement should be distinguished from uncomplicated bereavement, because patients with the latter need no treatment. In humans, there is evidence of increased adrenocortical activity and altered immune function following bereavement, whereas in non-human primates, biogenic amine systems appear to be involved in the response to maternal or social separation. According to a 'psychosomatic view of the brain', critical life events can both affect brain neurotransmitters and contribute to psychological and somatic symptoms of depression. Emotional events may be transduced into long-lasting brain changes, involving neurotransmitters, neuropeptides and receptors. Although only very limited evidence exists, long-term consequences could involve changes at the gene expression level.