In this paper, the ample experimental, clinical, genetic, histopathologic, and immunologic evidence for an important role of the gut in the pathogenesis of spondylarthropathy (SpA) and for an overlap between SpA and Crohn's disease is reviewed. These data suggest that SpA and Crohn's disease should be scientifically and clinically considered as distinct phenotypes of common immune-mediated inflammatory disease pathways rather than as separate disease entities. Classification, diagnosis, and therapy based on pathophysiologic insights is likely to become superior to an approach based exclusively on signs and symptoms, as evidenced by the recent evolution in treatment of SpA by tumor necrosis factor-a blockade.