There is a close association between psychological strain as well as psychological disorders and somatic diseases. Psychological impairments are embedded in a complex interacting model of somatic illnesses and psychological strain and not only a reaction due to physical disease. Comorbidity of depressive or anxiety disorders and medical diseases have been consistently reported in clinical studies whereas the association between substance abuse, somatoform disorders and eating disorders with chronic somatic disease has been examined less. This article describes relevant explanation models as well as risk factors, e. g. neurobiological, psychological and social factors, which have an impact on this association between mental disorders and chronic physical diseases. Moreover, etiological models for the comorbidity of oncological, cardiovascular and musculoskeletal diseases on the one hand and psychological disorders on the other hand are explained. Epidemiologic and family genetic investigation models will improve the knowledge about comorbidity in the future. Combining these approaches with neuroscientific and biopsychiatric models will enhance the knowledge about pathogenesis of comorbid disorders. Beside the scientific aim, the correct diagnosis and treatment of comorbid mental disorders is an important issue. Therefore improved diagnostics and treatment of psychological disorders has a substantial function in medical rehabilitation.