Specific recognition of foreign antigens and effective surveillance are the two mainstays of the body’s defense against microbial invasion. Evolution has created great antigen-receptor diversity and has equipped lymphocytes with exquisite motility and migratory properties to accomplish these tasks. As discovered more than four decades ago by Gowans and Knight, mature lymphocytes recirculate, moving continuously from blood to tissue and back to the bloodstream again.1 This recirculation is not random, but is guided by mechanisms allowing lymphocyte diapedesis at the correct site and directing their migration to the proper place in the tissues (for reviews, see 2-5]. Within the tissues, lymphocytes display a characteristic ‘amoeboid’ form of cell migration,6 which represents a physically optimized migration mode that allows easy cell traffic toward and between different tissue compartments. This movement is directed by chemokines and stromal cell networks in the lymphoid microenvironments.7,8 Lymphocyteendothelial recognition plays a central role in controlling the access of specialized lymphocyte subsets to particular tissues, thus influencing the nature of local immune and inflammatory responses. At the molecular level, this ‘homing’ process is regulated by adhesion molecules in concert with chemokines (chemoattractant cytokines): lymphocyte subsets as well as endothelial cells specifically program their expression of adhesion molecules and chemokines/chemokine receptors, allowing lymphocytes to move selectively to specific functional compartments of the immune system, such as the mucosal-associated lymphoid tissue (MALT) and the skin.2-5.