Our studies have shown that Salazopyrin EN is an effective slow-acting anti-rheumatic drug, improving clinical synovitis, depressing the acute phase response, capable of inducing remissions and possibly influencing the progression of joint damage. It is well-tolerated in the long-term with comparatively few serious side effects. Its mechanism of action, however, is still not entirely clear. We have found that the sulphapyridine moiety penetrates the synovial membrane and also that it can modify immune function. While Salazopyrin undoubtedly has an important role in the therapy of rheumatoid arthritis, it probably also has a place in the treatment of seronegative arthropathies and the spondyloarthritides. Furthermore we suggest that it should be used as an anchor drug in combination therapy to attempt to suppress disease activity further and limit joint damage.