The spondyloarthropathies are a group of human rheumatic disorders that are often associated with extra-articular features. Although a substantial number of studies is undertaken each year, many issues concerning the pathogenesis remain unanswered. There are several unresolved questions with regard to pathogenesis and treatment in spondyloarthropathies. First, the precise sites where inflammation originates within the joints have been a matter of controversy as enthesitis, synovitis and even bone marrow inflammation can occur during the course of spondyloarthropathies. In addition, the genetic predisposition involved in the origin of the close linkage between gut and joint inflammation, a prominent feature of SpA, has gathered much attention lately. Finally, whereas the effect of tumour necrosis factor (TNF) blockers in modulating inflammatory symptoms in SpA is well established, their ability to prevent new bone formation is much less certain. In addition, some marked differences appear to exist in the ability of the different TNF-blocking agents to modulate extra-articular disease manifestations.