Purpose of review - There is considerable interest in glutamine in both critical care and surgery. Glutamine offers the potential to enhance host defences and may reduce subsequent infections, hospital stay and mortality. This review will consider key papers in this field and update meta-analysis of this intervention in the light of new data. Recent findings - The current literature demonstrates that there are insufficient data to enable confident recommendations on the optimal route, timing, duration and dosage of glutamine. The Scottish Intensive care Glutamine or seleNium Evaluative Trial (known as the SIGNET trial) is the largest, critical care study of glutamine to date. This prospective, randomized controlled, factorial trial showed that glutamine administered as part of parenteral nutrition support does not decrease the number of new infections nor does it reduce mortality. Summary - To be able to confidently establish or refute the hypothesis that glutamine improves outcome in critical care, a well designed prospective randomized controlled trial is essential. To design such a trial, we require the optimal dose and duration of the nutritional supplement (balancing efficacy and toxicity, ease of administration and cost) and subsequently conduct an adequately powered trial. Such a trial is still lacking. © 2011, Nederlandse Vereniging voor Intensive Care.