The gut plays a key role in interorgan glutamine metabolism in normal and catabolic states. During critical illness, the gut responds to prevailing metabolic pressures that may result in a temporary "reset" in interorgan glutamine flow. As the body recovers from the disease process, the alterations in gut glutamine metabolism revert to normal, which helps restore glutamine homeostasis. Overwhelming stresses, such as severe systemic infection, may lead to permanent organ dysfunction and further adaptive changes in glutamine metabolism.