Immune system function depends on getting the right cells to the right place at the right time. Inadequate or inappropriate migration of immune cells is involved in many and perhaps all types of immunological disease. Chemokines have been identified as critical guidance factors that help recruit and position cells at each stage of the immune response. Two‐photon imaging of intact lymphoid organs has provided evidence of chemotactic migration of lymphocytes in lymphoid organs. Our work on the role of chemokines as organizers of lymphoid tissues will be briefly summarized. Lymphocyte egress from lymphoid organs is necessary for immune surveillance and for effector cell trafficking to sites of inflammation. Sphingosine‐1‐phosphate (S1P) receptor 1 and the circulatory lipid, S1P, are required for lymphocyte egress from lymphoid organs. We have recently identified CD69 as a regulator of S1P1 and controller of lymphocyte egress. Current molecular understanding of the lymphocyte egress process will be discussed.