Treatment of patients with ulcerative colitis (UC) has traditionally focused on improving symptoms, with the main objective of inducing and maintaining symptomatic remission. However, new evidence suggests that concentrating exclusively on clinical outcome measures may not be adequate to achieve long-term treatment success. Indeed, physicians should also be assessing the reduction of endoscopic activity, with the intention of achieving complete mucosal healing (defined as the absence of all mucosal ulceration, both microscopic and macroscopic, providing a sigmoidoscopy score of 0, as assessed on the Ulcerative Colitis Disease Activity Index). As a consequence of the customary reliance on symptomatic outcome measures, relatively few clinical trials have used mucosal healing or a composite including mucosal healing as a primary endpoint. This situation may soon change as new guidelines recommend the incorporation of mucosal healing into the primary endpoint of all new clinical trials in patients with UC. These recommendations are derived, in part, from data that have illustrated a correlation between mucosal healing and several important factors including long-term remission rates, disease-related complications (e.g., risk of colorectal cancer), healthcare utilization (e.g., need for colectomy), and patient quality of life. We already have drugs available to us that can effectively induce and maintain complete mucosal healing over long periods of time. This review evaluates the effect of medical therapy on mucosal healing in patients with UC and explores the importance of this outcome measure, both from the patient's perspective and clinical trial experience. Inflamm Bowel Dis 2009.