Relatively little was known about glutamine metabolism until the 1930s, when Sir Hans Krebs first demonstrated glutamine hydrolysis and biosynthesis in the kidney. Subsequent studies by Rose in 1938 demonstrated that glutamine is a nonessential (dispensable) amino acid, as it can be readily synthesized de novo in virtually all tissues in the body. Because the body has the capacity to synthesize considerable quantities of glutamine, it has been assumed that glutamine is not required in the diet. However, this amino acid becomes quite depleted during the course of a catabolic insult such as injury or infection, indicating that the ability of glutamine production to meet demands during a variety of surgical illnesses is impaired. In states of health, the assumption that glutamine is not required in the diet is probably valid, although it is difficult to test the hypothesis, as glutamine is present in virtually all dietary proteins. Most naturally occurring food proteins contain 4% to 8% of their amino acid residues as glutamine; therefore less than 10 g of dietary glutamine is likely to be consumed daily by the average person. In contrast to this usual dietary availability, studies in stressed patients indicate that considerably larger amounts of glutamine (20-40 g/day) may be necessary to maintain glutamine homeostasis. Thus from a nutritional standpoint, glutamine may be thought of as a drug as well as a nutrient. This paper reviews the physiology and biochemistry of glutamine with an emphasis on its metabolism in surgical illnesses and its role as a conditionally essential amino acid.