Crohn disease (CD) and ulcerative colitis (UC) comprise a group of inflammatory disorders of the gastrointestinal tract that can vary in severity of disease, anatomic extent of inflammation, presence and nature of extraintestinal manifestations, and response to therapeutic approaches. There have been attempts to classify CD based on the location and behavior of disease. Advances in understanding of genetic susceptibility to inflammatory bowel disease (IBD) suggest that CD and UC may represent a continuum of overlapping disorders. This has led to an attempt to classify IBD on clinical, molecular, and serologic grounds. Differences in clinical, genetic, and immunologic profiles may require more targeted, refined treatment approaches to help clinicians make decisions regarding recently introduced biologic agents. This article provides an overview of the current approaches to therapy for CD and UC and focuses on the evidence supporting the rationale for changing paradigms in the management of IBD, including mucosal healing as an end point and earlier use of immunosuppressive and biologic agents, particularly in CD (so-called top-down therapy).