Biologic therapy includes many different categories of agents targeted to diverse mechanisms of disease. Recently, a host of novel biologic therapies have been developed to attack a wide variety of immunologic and inflammatory mechanisms. These include recombinant cytokines and growth factors; monoclonal antibodies against cytokines, accessory molecules, and cellular adhesion molecules; nucleotide-based therapies; and cell and gene therapies. Among the biologic agents recently reported to have been prospectively studied in patients with inflammatory bowel disease are monoclonal antibodies against CD4 and tumor necrosis factor, and interleukins 10 and 11. Many other biologics have been examined in other immune-mediated diseases in humans, and in animal models of colitis. This review surveys the rationale and use of biologic therapies in inflammatory bowel disease.