During stress conditions such as multiple trauma and critical illness, the demand for glutamine increases and its concentration in plasma and muscle falls dramatically. Therefore, glutamine has been re-classified as an essential amino acid under such catabolic conditions. The role of glutamine supplementation in trauma patients has been extensively studies. Despite the numerous clinical trials that investigated the effect of enteral and parenteral glutamine supplementation in multiple trauma patients, the results are inconclusive. Glutamine supplementation through parenteral route has been associated with reduced infectious complications, mortality, costs and hospital length of stay. However, glutamine supplementation in multiple trauma patients receiving enteral nutrition and its best route are still controversial. Although glutamine supplementation is recommended in multiple trauma patients, large well designed multi-centre trials are required to provide a confirmed conclusion.