Caloric restriction has been the subject of intensive research and is known to be the most efficacious means of increasing longevity and reducing pathology. Caloric restriction has been found to influence a wide variety of age-sensitive immunological parameters such as interleukin-2 (IL-2) gene expression, and overall, the immunological status of rodents fed a caloric restriction diet is superior to the immunological status of the non-restricted animals. IL-2 is a growth promoting cytokine that plays a critical role in immune function. The expression of IL-2 has been shown to decrease with age, and the decrease in IL-2 expression parallels the age-related decrease in immune function. The focus of this review article is to discuss the studies on the influence of caloric restriction on IL-2 expression and the recent findings on the mechanisms by which caloric restriction enhances IL-2 gene expression. A number of studies have demonstrated that caloric restriction alters the expression of the IL-2 gene at the level of transcription. The increase in IL-2 expression correlates with an increase in binding activity of the transcription factor NFAT which plays a predominant role in IL-2 transcription. In addition, preliminary results suggest that activation of the upstream signaling molecules, the mitogen-activated protein kinase (MAPK) signaling cascade, may play a role in the enhancement of IL-2 transcription.