Standard of care for ulcerative colitis involves long-term pharmacotherapy or colectomy. Approximately 20% to 30% of patients eventually require a colectomy because patients either do not respond or cannot tolerate the currently available pharmacotherapies. Advances in our knowledge of the pathophysiology of ulcerative colitis have highlighted the importance of cytokines such as tumor necrosis factor alpha (TNFα) in the inflammatory process. TNFα is a proinflammatory mediator that plays an integral role in the pathogenesis of inflammatory bowel disease. In addition, mounting evidence indicates a genetic association between TNFα and ulcerative colitis. Furthermore, increased TNFα levels have been demonstrated in studies of patients with ulcerative colitis. TNFα is likely an important component in the pathophysiology of ulcerative colitis, and thus agents targeting TNFα in ulcerative colitis have been studied. Recent randomized controlled trials have confirmed that biologic anti-TNFα therapy is effective in ulcerative colitis. Soluble TNFα receptors or biologic agents that suppress or inhibit TNFα production may also show therapeutic promise.