Encounters between physicians and patients from different cultural backgrounds are becoming commonplace. Physicians strive to improve health outcomes and increase quality of life for every patient, yet these discordant encounters appear to be a significant factor, beyond socioeconomic barriers, in creating the unequal and avoidable excess burden of disease borne by members of ethnic minority populations in the United States. Most clinicians lack the information to understand how culture influences the clinical encounter and the skills to effectively bridge potential differences. New strategies are required to expand medical training to adequately address culturally discordant encounters among the physicians, their patients, and the families, for all three may have different concepts regarding the nature of the disease, expectations about treatment, and modes of appropriate communication beyond language. The authors provide an anthropological perspective of the fundamental relationship between culture and health, and outline systemic changes needed within the social and legal structures of the health care system to reduce the risk of cross-cultural miscommunication and increase the likelihood of improving health outcomes for all populations within the multicultural U.S. society. The authors define the strengths inherent within every culture, provide a guideline for the clinician to evaluate disease and illness within its cultural context, and outline the clinical skills required to negotiate among potential differences to reach mutually desired goals for care. Last, they indicate the structural changes required in the health care setting to enable and support such practice.