Glutamine is a non-essential amino acid which is produced in sufficient amount by the healthy human body. From experimental work it is known that glutamine is an important nutrient for rapidly dividing cells such as cells from the immune system and the gut. During several conditions a lack of glutamine may occur. This will result in functional disturbances of the immune system and/or the gut. Glutamine is produced mainly by the muscle tissue. A decrease in muscle mass during nutritional depletion may result in decreased glutamine production capacity. Furthermore during critical illness, there is an increased demand for glutamine probably as a result of an increased utilization by the immune system. In addition, patients receiving standard parenteral nutrition do not receive glutamine, until recently, commercial parenteral nutrition did not contain glutamine because of instability of this amino acid during prolonged storage. One of the important functions of the gut is to prevent migration of bacteria and/or toxins from the gut lumen into the systemic circulation. A lack of glutamine may result in deterioration of this intestinal barrier. Supplementation of glutamine to certain patients could be essential. The relation between glutamine and the gut in several situations (nutritional depletion, critical illness, parenteral nutrition) is discussed in this paper.