Background: Since the pathophysiology of medically unexplained symptoms (MUS) remains unclear, health care providers often struggle with these patients, especially with a different ethnic and/or cultural background. These challenges are insufficiently addressed in their training and in the organization of care. Aim: To improve health care provider-patient interaction focused on MUS patients in general and in ethnic minorities and refugees in particular through a systematic review of syndromal definitions and epidemiology and organization of care of MUS patients. Methods: Screening of PubMed, Web of Science, Cinahl and Cochrane Library on the keywords ‘Medical unexplained (physical) symptoms (MUPS)’, ‘Somatoform disorder’, ‘Functional syndrome’, ‘Diversity’, ‘Migrants’, ‘Ethnicity’, ‘Care models’, ‘Medical education’, ‘Communication skills’, ‘Health literacy’ Results: Different case definitions result in markedly different epidemiologic estimates for MUS patients. Nevertheless, they are prevalent in a wide range of health care settings. Literature offers evidence of the effectiveness of structural frameworks in approaching MUS patients. Organization of MUS care needs to transcend different levels of care: specialist tertiary and secondary care and primary care involving different qualifications of caregivers need to be aligned. Conclusion: The systematic review identified significant gaps and shortcomings in organization of care. These need to be addressed in order to improve outcomes. Keywords: Medical unexplained (physical) symptoms (MUPS), Somatoform disorder, Functional syndrome, Diversity, Migrants, Ethnicity, Care models Message for the clinic: - Medically unexplained symptoms are highly prevalent but case definitions hamper both recognition and a proper approach. - MUS are ill understood in both the general population as in migrants and refugees. - Interdisciplinary and integrated care through a biopsychosocial model is mandatory.