Glutamine, the most abundant amino acid in the body, is thought to become conditionally essential in critical illness. Some of the important roles for glutamine are as a carrier for inter-organ N, a preferred fuel for enterocytes and cells of the immune system, a substrate for renal NH3 formation and a precursor for glutathione. Mechanisms by which glutamine could improve recovery include attenuating oxidant damage and inflammatory cytokine production, reducing gut bacterial translocation and improving N balance. The present systematic review has found trends to suggest that parenteral and enteral glutamine supplementation reduce mortality, the development of infection and organ failure in critical illness. Trials of parenteral nutrition containing glutamine with patients after elective surgery also suggest reduction of infection, but it is unlikely that glutamine-containing parenteral nutrition would be used for such patients. The evidence base is limited by the quality of the reported trials and the suggestion that there is publication bias, with trials suggesting reduced infection being more likely to be published.