There are clear differences in the clinical picture and in the pathogenesis between rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Biologic agents targeting TNF-alpha are efficacious in both diseases, with some tendency to work even better in spondyloarthritides (SpA) on a clinical basis. However, anti-TNF therapy was shown to inhibit radiographic progression in RA but not in AS. This is probably due to the outstanding difference in pathogenesis: while in RA osteodestructive lesions such as erosions predominate, AS patients will rather develop osteoproliferative changes such as syndesmophytes. There is some evidence that anti-TNF agents may show longterm efficacy and acceptable safety profiles over 5-10 years. There are some differences between the agents.Whether the recent developments of targeted therapies in RA with agents such as rituximab, abatacept and tocilizumab will also work for AS is unknown at present.