Several investigators as well as an NIH consensus conference on the “irritable bowel syndrome” (IBS) have stressed the importance of the biopsychosocial model in the etiopathogenesis (origin and development) of this syndrome. In this short article, the pathophysiologic (disease process) links between big brain, little brain, motility and sensation are explored based on currently available data. These data suggest that investigators and clinicians need to be dissuaded from approaching IBS as though it was a single disorder in all patients, or as though only one mechanism is responsible for development of symptoms. In essence, this is a plea for the importance of integrated rather than reductionist approaches to research, diagnosis, and management of IBS. Revised and updated 2009.