An association between mental disorders, musculoskeletal and cardiovascular diseases has been reported in many clinical studies with inpatients. However, no data exist about the prevalence of mental disorders in patients undergoing rehabilitation treatment for musculoskeletal and cardiovascular diseases. The present study investigates 4-week, 12-month and lifetime prevalence rates of comorbid mental disorders in more than 1700 patients out of 10 rehabilitation clinics. The patients were screened (GHQ-12, HADS) in the context of a two-stage epidemiological survey. In the second-stage examination a subsample of 369 patients was interviewed with a standardized clinical interview (CIDI) in order to obtain DSM-IV and ICD-10 diagnoses of mental disorders. 43 % (musculoskeletal) and 36 % (cardiovascular) of the patients have high GHQ-scores (cut off > 4). Furthermore, up to 24 % of the musculoskeletal and cardiovascular patients have elevated scores on the HADS subscales depression and anxiety (cut off > 10). For the 4-week period, prevalence rates of mental disorders in the sample of patients with musculoskeletal diseases are 31 % and 20 % in the sample of patients with cardiovascular diseases. The most frequent current disorders are affective and anxiety disorders. The high psychosocial burden expressed by the patients and the prevalence of depressive and anxiety disorders emphasize the importance of (1) effective diagnostic strategies to recognize mental disorders, (2) specialized psychological services in rehabilitation clinics, which provide psychological support and effective interventions for patients with musculoskeletal and cardiovascular diseases.