Supplementation of the conditionally essential amino acid glutamine may be beneficial for individuals who are highly stressed and have minimal energy and protein reserves. This includes elderly individuals, postoperative patients, individuals with cancer and very low birthweight infants. Individuals who are undergoing treatment with catabolic glucocorticoids may also benefit. Unfortunately, confusion exists as to situations in which glutamine may be beneficial because a clearly defined "glutamine deficiency syndrome" has not been described as for some other nutrients. In this review, we will discuss how glutamine affects protein metabolism under certain stressful conditions, how it affects intestinal mucosal integrity and how this might relate to sepsis and systemic inflammation. We will also discuss nutrients that are closely related to glutamine such as glutamate, nucleotides, arginine, glucosamines, and ornithine alpha-ketoglutarate and how and why they might be used as substitutes for glutamine.