After many decades debating whether the clinical manifestations of patients with functional digestive symptoms originate "in their minds" or "in their guts," arguments remain strong on both sides of the controversy. However, advances in understanding of gut physiology and pathophysiology, and persuasive evidence on the bidirectionality of the regulatory traffic between the enteric and central nervous systems, are helping to characterize clinical situations in which we can legitimately speak of gut dysfunction, as opposed to others where symptoms are not associated with apparent or detectable gut disturbances and may truly represent somatization of an affective disorder. In this review, we describe available clinically applicable technology, albeit in specialized clinical research units, that may be used to discern whether or not challenging patients have gut sensory or motor disturbances. The practical yield of applying such methods to diagnostic investigation may be substantial, because it establishes a plausible mechanism of disease that may be used in patient management and patient persuasion, to remove uncertainties and to prevent futile repetition of conventional diagnostic tests. By evolving from symptom analysis to mechanism-based diagnosis, our gastroenterology community may progress toward the goal of delivering the full diagnostic spectrum from altered morphology to disturbed function.