Although both rheumatoid arthritis (RA) and ankyosing spondylitis (AS) belong to the group of chronic inflammatory rheumatic diseases, they are quite different regarding mechanisms of inflammation and repair. While RA is an erosive destructive disease with the synovium as the primary site of inflammation, the immune response in AS takes place primarily at the cartilage/bone interface, and the pathological but also the clinical picture is determined by an until not yet well defined interaction between inflammation and new bone formation. Most recently, first insights into the molecular mechanisms between inflammation and bone destruction or new bone formation could be obtained. Key molecules involved in bone homeostasis seem to differ between RA and AS patients. While the molecules sclerostin and dickkopf 1, both inhibitors of osteoblasts, are elevated in RA they are found to be rather low in AS. It can be expected that the rapidly expanding new field of osteoimmunology will help to clarify the pathogenesis of the these two diseases with possible implications for new treatment targets.