There continue to be evolutionary changes in the management of ulcerative colitis despite the fact that, aside from a variety of aminosalicylate formulations, no new therapies have been approved over the past few decades. Nevertheless, debates continue regarding the optimization of treatment with aminosalicylates and the short- and long-term benefits of immunomodulation in ulcerative colitis. This article focuses on the most recent clinical studies pertaining to the management of ulcerative colitis and explores both the advances and controversies pertaining to aminosalicylate therapy, corticosteroids, cyclosporine, and the purine antimetabolites. Novel therapeutic approaches—including preliminary experience with biological therapies directed at tumor necrosis factor and other cytokines, adhesion molecules, growth factors, and probiotics—will be reviewed. Recent data regarding potential chemoprevention in long-standing ulcerative colitis and management of postoperative complications and pouchitis will also be discussed.