Patients with cancer have an impaired T‐cell response that can decrease the potential therapeutic benefit of cancer vaccines and other forms of immunotherapy. l‐arginine (l‐Arg) is a conditionally essential amino acid that is fundamental for the function of T lymphocytes. Recent findings in tumor‐bearing mice and cancer patients indicate that increased metabolism of l‐Arg by myeloid derived suppressor cells (MDSCs) producing arginase I inhibits T‐lymphocyte responses. Here we discuss some of the most recent concepts how MDSC expressing arginase I may regulate T‐cell function in cancer and other chronic inflammatory diseases and suggest possible therapeutic interventions to overcome this inhibitory effect.