The homeostasis of the immune system is maintained by the recirculation of naive lymphocytes through the secondary lymphoid tissues, such as the lymph nodes, Peyer's patches and spleen. Upon antigen encounter in the secondary lymphoid tissues, lymphocytes become activated and undergo a reprogramming of their trafficking properties. Most antigen-experienced lymphocytes traffic through the secondary lymphoid organs, but they can also migrate to extralymphoid tissues, where they exert effector functions. Dendritic cells in the secondary lymphoid tissues are crucial for the reprogramming of trafficking properties of activated T-lymphocytes. The exquisite specificity of such lymphocyte trafficking is determined by tissue-specific guidance signals expressed by the vascular endothelial cells, combined with counter receptors expressed by circulating lymphocytes. The high endothelial venules can selectively recruit naive lymphocytes into the lymph nodes and Peyer's patches by expressing a unique combination of vascular addressins and chemoattractants. The inflamed postcapillary venules in extralymphoid tissues also use a distinct array of endothelial adhesion molecules and tissue selective chemokines to support the recruitment of effector and memory lymphocytes that express appropriate trafficking receptors. Exit of lymphocytes from lymphoid and extralymphoid tissues into circulation is actively regulated by signals through specific receptors for sphingosine-1-phosphate and a certain chemokine(s), respectively. This review summarizes the present understandings of the mechanisms regulating homeostatic recirculation of naive lymphocytes through the secondary lymphoid tissues and tissue-specific trafficking of antigen-experienced lymphocytes.