In the last years the therapeutic goals of inflammatory bowel disease have changed from control of symptoms only towards long term strategies aimed at modifying the natural history of the disease. In this setting mucosal healing has emerged as an important therapeutic goal both in clinical trials and in clinical practice. Growing evidence suggests that mucosal healing may be associated with lower relapse rates, reduced hospitalizations and reduced need of surgery both in ulcerative colitis and in Crohn's disease. However, a validated definition of mucosal healing is lacking: as a consequence, although several drugs are capable of inducing and maintaining mucosal healing in different clinical settings, the effect size of different treatments is difficult to assess. One of the most important question for clinical practice is if we should systematically assess mucosal healing in all patients and target our treatment strategies to achieve mucosal healing. This review focuses on the definition of mucosal healing and on the ability of different medications to induce and maintain mucosal healing in inflammatory bowel disease. The significance of mucosal healing as a surrogate end point of disease outcome is also discussed.