Purpose of review A recent editorial. proclaimed, 'Glutamine, a life saving nutrient, but why?' This review will assess if recent data support glutamine as a life-saving nutrient in critical illness, and, if so, utilize new understanding of gene-nutrient interactions to address potential mechanisms by which glutamine may be 'life-saving'. Recent findings Updated meta-analysis data reveal that glutamine appears to exert a beneficial effect on mortality in critical illness. The questions remaining to be answered regard in what settings and via what method of administration does this phamaconutrient show optimal benefit? It is likely that examination of molecular mechanisms by which glutamine functions will lead to an understanding of how best to utilize glutamine as a pharmacologic agent. Recent laboratory data reveal that these mechanisms include tissue protection, attenuation of inflammation, improved tissue metabolic function, and attenuation of oxidant stress. Summary Glutamine may be potentially 'life-saving' in critical illness, particularly when administered in doses greater then 0.3 g/kg/day. Present data indicate that,glutamine functions as a 'stress signaling molecule' following illness/injury and thus, needs to be given as a pharmacologic agent, rather then as nutritional replacement. Presently, multicenter clinical trials utilizing glutamine as a drug, independent of nutritional needs, are indicated.