A typical immune response to infection by a microbe results in rapid amplification and subsequent differentiation of a few antigen-specific naïve lymphocytes into many effector lymphocytes. Upon antigen exposure, these effector T or B cells rapidly secrete large amounts of either lymphokines (cytokines produced by lymphocytes) or soluble antibodies, respectively. Although the vast majority of these effector cells die after antigen clearance, some cells survive as memory cells and give lifelong protection to the host against a second infection by the same microbe. It has been appreciated for years that memory cells respond more rapidly than do naïve lymphocytes; however, the molecular mechanisms controlling memory cells remain largely unknown. A study now shows that abundance of the transcription factors nuclear factor of activated T cells c1 and c2 (NFATc1 and NFATc2) is much higher in memory (and effector) T cells than in naïve T cells. This suggests that NFATs have an important function in memory T cells but leaves open the questions of which transcription factors control interleukin-2 (IL-2) synthesis in naïve T cells and which mechanisms generate the high abundance of NFAT in memory T cells.