Lymphocyte migration (homing) to specific tissues has an important role during protective and pathological immune responses, including inflammatory bowel diseases. Lymphocytes use integrin α4β7 and the chemokine receptor CCR9 to localize to the gastrointestinal mucosa; their respective ligands, mucosal addressin cell adhesion molecule-1 and CCL25, are displayed on endothelial cells in intestinal postcapillary venules. Although gastrointestinal-homing receptors are required for lymphocyte migration to the intestine in the noninflamed steady state, their role during inflammation is a matter of debate. Reagents designed to block interactions between these receptors and their ligands have had variable degrees of success in animal models of inflammatory bowel diseases and patients. We discuss the mechanisms involved in lymphocyte localization to the intestinal mucosa and how they can be applied to therapy for inflammatory bowel diseases.