Glutamine (GLN) has been shown to be a key pharmaconutrient in the body's response to stress and injury. It exerts its protective effects via multiple mechanisms, including direct protection of cells and tissue from injury, attenuation inflammation, and preservation of metabolic function. Data support GLN as an ideal pharmacologic intervention to prevent or treat multiple organ dysfunction syndrome after sepsis or other injuries in the intensive care unit (ICU) population. A large and growing body of clinical data shows that GLN can be a life-saving intervention in well-defined critically ill patient groups. Recent data has helped clarify that GLN shows the greatest benefit when administered at doses greater than 0.35 g/kg/day, with optimal benefit potentially occurring at 0.5 g/kg/day. Further, it appears that when possible GLN should be administered for longer than 5 days and more ideally for the entire period of ICU or hospital stay. Finally, ongoing clinical trials may prove GLN administration in the first 24-48 h following ICU admission and via both the enteral and parenteral route are key to optimizing patient outcomes with this therapy.