The dysregulated recruitment of leukocytes into the intestine is required for the initiation and maintenance of inflammatory bowel disease (IBD). Several families of molecules regulate the influx of these cells into sites of inflammation. Interference with some of these molecules has already shown efficacy in the clinics and antibodies that target the molecules involved have been approved by the FDA for use in Crohn's disease (CD), multiple sclerosis (i.e., natalizumab), and psoriasis (i.e., efalizumab). Here, we discuss basic aspects of the different families of relevant molecules and compile a large body of preclinical studies that supported the targeting of specific steps of the leukocyte adhesion cascade for therapeutic purposes in colitis and in novel models of CD-like ileitis.