Since the initial observations that highlighted the importance of lymphocyte trafficking for immune responses, the pathways utilized by B and T lymphocytes to recirculate and properly position themselves have been intensely studied. Most of the chemoattractants along with their cognate receptors that affect lymphocyte trafficking have been identified. Some of their functions are promotion of lymphocyte ingress into immune organs, localization of cells to specific regions within those organs, maintenance of lymphocyte basal motility in immune organs, facilitation of lymphocyte egress from these organs, and control of migration and homing of lymphocytes in the periphery. Since the seminal discovery that agonism of sphingosine-1-phosphate receptors evokes changes in lymphocyte homing and trafficking, considerable effort has been undertaken to characterize the mechanism utilized by these receptors to influence lymphocyte behavior. This review will focus on the influence of sphingosine-1-phosphate signaling system on lymphocyte localization, egress from lymph organs, and its effects on the lymphatic vasculature.