Currently, the therapeutic end-point in the treatment of Crohn's disease is the remission of symptoms, but recent data confirm that mucosal inflammation may continue in the absence of symptoms. Furthermore, emerging evidence indicates that such subtle, sub-clinical mucosal inflammation leads to clinical relapse. The assessment of mucosal inflammation has become easier with the availability of faecal calprotectin assay. Current anti-inflammatory therapy often leaves low-grade mucosal inflammation untreated, and therefore recurrent relapses occur. We need to investigate whether the therapeutic end-point of anti-inflammatory medications needs to be more rigorous and to aim at complete mucosal healing, confirmed by the normalization of mucosal inflammatory markers such as faecal calprotectin concentrations. Immunosuppressive therapy with azathioprine/ 6-mercaptopurine currently offers the best mucosal healing treatment with reduction of relapses, but newer biological agents might offer less toxic therapy. Clinical trials to test the feasibility and efficacy of such a paradigm shift in the medical management of Crohn's disease are now warranted.