Amino acids are essential for protein synthesis, epigenetic modification through the methylation of histones, and the maintenance of a controlled balance of oxidoreduction via the production of glutathione and are precursors of certain neurotransmitters. T lymphocytes are particularly sensitive to fluctuations in amino acid levels. During evolution, the production of amino-acid catabolizing enzymes by mainly antigen-presenting cells has become a physiological mechanism to control T-cell activation and polarization. The action of these enzymes interferes with TCR and co-stimulation signaling, allowing tuning of the T-cell response. These capacities can be altered in certain pathological conditions, with relevant consequences for the development of disease. Introduction The activation of antigen-specific T lymphocytes drives them from quiescence to rapid clonal expansion, accompanied by effector differentiation. These profound functional modifications are permitted by rapid changes in metabolic programming to fulfill the abrupt increase in the requirement of nutrients and energy. Thus, lymphocytes are particularly vulnerable to alterations of the metabolic microenvironment.