Some people consume chronically glutamine (GLN) in high quantities (~40 g/d), although a number of biochemical pathways and cellular functions may be negatively affected. The following side effects of GLN supplementation are discussed: (1) Alterations in amino acid transport-as GLN shares the transporters with other amino acids, enhanced GLN intake may impair amino acid distribution among tissues and their absorption in the gut and kidneys. (2) Alterations in GLN metabolism-GLN supplementation may impair synthesis of endogenous GLN and enhance glutamate and ammonia production. (3) Alterations in ammonia transport-GLN supplementation may impair ammonia detoxification and negatively affect the role of GLN as the carrier of ammonia among tissues. (4) Abnormalities in aminoacidemia-increased plasma levels of GLN, glutamate, citrulline, ornithine, arginine, and histidine and decreased levels of valine, leucine, isoleucine, glycine, threonine, serine, and proline are reported. (5) Alterations in immune system-as GLN has immunomodulating properties, the effect of chronic GLN consumption on the immune system needs to be assessed. (6) Effect on tumor growth-it should be elucidated whether chronic intake of GLN increases the risk of cancer. (7) Effect of the withdrawal of GLN supplementation-due to the adaptive response of the organism to enhanced GLN consumption, the withdrawal of GLN may enhance the risk of health problems resulting from GLN deficiency. It is concluded that enhanced intake of GLN has substantial side effects, and long-term studies should be performed to justify chronic consumption of a GLN-enriched diet.