There is evidence from some prospective and several retrospective studies that early biological and psychosocial stress in childhood is associated with long-term vulnerability to various mental and physical diseases. In the last few years research findings have accumulated on those emotional, behavioural and psychobiological factors which are responsible for the mediation of these lifelong consequences. They are the cause of an increased risk of somatization and other mental disorders. Particularly anxiety, depression and personality disorders often result in high-risk behaviour that itself is associated with physical disease (cardiovascular disorders, stroke, viral hepatitis, type 2 diabetes, chronic lung diseases) as well as with aggressive behaviour. A survey on the current knowledge of how these various factors interact is presented and a bio-psychopathological model of vulnerability is educed. Implications for future research are outlined and contrasted to actual political trends in Germany.