Recent evidence suggests that there is a link between increased colonic inflammation and risk of colorectal cancer, stressing the importance of preventing relapse. The risk of relapse is associated with several factors, of which the foremost is patient nonadherence to prescribed medical therapy. Nonadherence may be affected by such factors as complicated dosing regimens, forgetfulness, male sex, and treatment delivery methods. Mesalamine is the standard, first-line therapy and the treatment of choice for inducing and maintaining clinical and endoscopic remission of inflammation in patients with mild-to-moderate ulcerative colitis. Novel formulations of mesalamine and newly devised, high-dose regimens offer additional therapeutic options and may lead to improved treatment adherence, longer-lasting periods of remission, and enhanced patient well-being.