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The derivation of and concepts underlying the biopsychosocial model have not been well explained. This model does not relate psychosocial processes to illness in a linear fashion (e.g., as “psychogenic” or “psychophysiologic”). Rather, the model considers the degree to which factors interact to explain an illness condition. As an example, the irritable bowel syndrome is not caused by a single etiology. Rather, it may result from dysregulation of central and enteric nervous system (CNS/ENS) function manifest as dysmotility and/or visceral sensitivity, and modified by psychosocial processes, all of which uniquely determine the experience of the illness. In this discussion, I trace the derivation of the biopsychosocial model and its application in modern gastroenterologic research and clinical practice.