The evolutionarily conserved febrile response has been associated with improved survival during infection in endothermic and ectothermic species although its protective mechanism of action is not fully understood. Temperatures within the range of physiologic fever influence multiple parameters of the immune response including lymphocyte proliferation and cytotoxic activity, neutrophil and dendritic cell migration, and production or bioactivity of proinflammatory cytokines. This review focuses on the emerging role of fever-range thermal stress in promoting lymphocyte trafficking to secondary lymphoid organs that are major sites for launching effective immune responses during infection or inflammation. Specific emphasis will be on the molecular basis of thermal control of lymphocyte-endothelial adhesion, a critical checkpoint controlling lymphocyte extravasation, as well as the contribution of interleukin-6 (IL-6) trans-signaling to thermal activities. New results are presented indicating that thermal stimulation of lymphocyte homing potential is evident in evolutionarily distant endothermic vertebrate species. These observations support the view that the evolutionarily conserved febrile response contributes to immune protection and host survival by amplifying lymphocyte access to peripheral lymphoid organs.