Although the thymus plays a key role in T cell maturation in mammals, it begins to atrophy and involute at sexual maturity. The diminished thymic microenvironment is thought to contribute to reduced adaptive immune function during aging, leading to the increased likelihood of infectious diseases and cancer. Caloric restriction or ectopic expression of the pro-longevity growth factor fibroblast growth factor 21 has been reported to maintain the thymus in aging mice. Moreover, forced expression of the transcription factor FoxN1 has been shown to rejuvenate thymuses from old mice almost completely, restoring their youthful state. These results open the way for development of potential drugs to restore immune function in the elderly.