Amino acids are not only the building blocks of proteins but are also key regulators of various pathological and physiological processes, including immune responses, in living cells. However, the mechanisms responsible for these effects of amino acids are largely unknown. The regulatory roles of amino acids in the immune system can be considered from two perspectives, namely, the enhancement of the immune response that protects individuals from infections and malignant neoplasms, and the reduction of over-responses such as inflammation and autoimmunity. In this review, we focus on the regulatory roles of amino acids in the immune response, showing how several amino acids (e.g., glutamine, arginine, tryptophan, cystine/cysteine, glutamate, and branched-chain amino acids) enhance immunity. Additionally, we describe how one amino acid, histidine, functions as an anti-inflammatory agent in colitis.