Biological therapies are being increasingly investigated for the treatment of inflammatory bowel disease. However, a great deal more study has been devoted to studies of Crohn's disease rather than ulcerative colitis. Ulcerative colitis, like Crohn's disease, represents an area of high clinical need, particularly for those patients who have disease inadequately responsive to corticosteroids and 5-aminosalicylates. The distinct anatomic distribution of inflammation in ulcerative colitis represents an important model for study, with the entire involved mucosa entirely accessible to endoscopy. In addition, there is an opportunity for local delivery of biologic agents in left-sided disease. Distinct pathogenetic factors in ulcerative colitis raise the possibility of therapies quite different from those used in Crohn's disease. This work describes the current state of knowledge regarding biological therapy in ulcerative colitis. The role of probiotic therapy, and studies of cytokine-directed therapies, therapies targeting adhesion and recruitment, and restitution and repair are described.