During progression, tumors become refractory to the offensive weapons of the immune system. It has been known for a long time that the tumor microenvironment presents a profound modification in the metabolism of arachidonic acid and amino acids such as l-triptophan and l-arginine. However, only in the last decade we have started to appreciate how these changes might cause dysfunctions in cells of both adaptive and innate immune system. The knowledge of these complex and partially interconnected metabolic pathways is offering new targets for an integrated pharmacological approach aiming at freeing tumor-specific T lymphocytes from the latches of cancer influence.