In contrast to rheumatoid arthritis (RA), the concept of disease modification in ankylosing spondylitis (AS) remains to be clarified. Endpoint measures employed in AS trials primarily assess features related to symptomatology while endpoints considered more relevant to the concept of disease modification, such as spinal mobility, acute-phase reactants and radiological progression, either lack sensitivity to change or have not been comprehensively validated. NSAIDs alleviate symptoms of AS but most trials have been short term, precluding meaningful conclusions regarding disease modification. Among disease-modifying therapies used in RA, sulfasalazine has been studied in several controlled trials mostly in patients with longstanding disease, effect sizes being small and limited to those with peripheral synovitis. No conclusions can be drawn from the limited studies evaluating methotrexate.