Spondyloarthropathies (SpA) are a group of related disorders with common clinical and genetic characteristics. The prototype disease in this group is ankylosing spondylitis; other entities include reactive arthritis, psoriatic arthritis, and arthritis in patients with inflammatory bowel disease. Over recent years, there has been a special interest in the relation between spondylitis/synovitis and gut inflammation in patients with SpA. Two thirds of patients with undifferentiated SpA show histologic signs of gut inflammation, and a fraction of these patients go on to develop clinically overt Crohn's disease. In this review, the authors will focus on 1) the growing evidence that has been provided that gut inflammation in SpA is immunologically related to Crohn's disease, based on the molecular characterization of the inflammation (lymphocyte homing markers and ligands, T cell cytokines, macrophage markers, and serology); and 2) on the therapeutic implications resulting from this concept. The recent introduction and positioning of anti-tumor necrosis factor-alpha therapy in patients with ankylosing spondylitis and other types of SpA is, in large part, based on this concept.