Differentiation of immature T and B cells in the primary lymphoid organs gives rise to a pool of long-lived lymphocytes that recirculate through the secondary lymphoid tissues. On the basis of their surface markers, T and B cells comprise a mixture of naïve and memory cells with differing life-spans. Immunization (and vaccination) causes naïve lymphocytes to proliferate and differentiate into effector cells and memory cells. Whether the survival of memory cells is innate or requires persistent contact with residual antigen is controversial. Resolving this issue may be crucial for designing optimal vaccines.