Activation of a naïve T cell is a highly energetic event, which requires an increase in metabolism. Upon stimulation, T cells increase in size, rapidly proliferate and differentiate, all of which lead to a high demand for energetic and biosynthetic precursors. Even though amino acids are the basic building blocks of protein biosynthesis, the role of amino acid metabolism in this process has not been well characterized. We have found that glutamine in particular is required for both proliferative as well as effector function. We have evidence that glutamine regulates ERK signaling and that ERK in turn may also regulate glutamine transport. These data indicate that glutamine may play a significant role in T cell signaling and that a better understanding of glutamine utilization in T cells may reveal novel targets for immunomodulatory and/or anti-leukemia therapy.