OBJECTIVE: This review will attempt to summarize recent clinical data on glutamine's use. It will present the concept of glutamine as a "drug" or "nutraceutical," given in addition to standard nutrition support. Key references will be discussed, and clinical recommendations with regard to patients who may benefit and dosing are also provided. RECENT FINDINGS: Glutamine, traditionally considered a nonessential amino acid, now is considered "conditionally essential" after critical illness, stress, and injury. States of illness or injury can lead to a significant decrease in plasma levels of glutamine, and when this decrease is severe, it has been correlated with increased mortality. Laboratory data have demonstrated numerous benefits of glutamine in experimental models of critical illness, cancer, and cardiac injury. The mechanism of these protective effects includes attenuated proinflammatory cytokine expression, improved gut barrier function, enhanced ability to mount a stress response, improved immune cell function, and decreased mortality. Over the last 10 years, clinical trials of glutamine supplementation in critical illness, surgical stress, and cancer have shown benefit with regard to mortality, length of stay, and infectious morbidity. However, data demonstrating a lack of benefit with glutamine supplementation in some patients have been presented as well. It appears that dose and route of administration clearly influence the benefit observed from glutamine administration, with high-dose parenteral glutamine demonstrating an advantage over low-dose enteral glutamine. SUMMARY: High-dose or parenteral (> 0.25 to 0.30 g/kg/day IV or >or=30 g/day enterally) glutamine appears to demonstrate the greatest potential for benefit in hospitalized patients. No evidence of harm has been observed in studies conducted to date; thus, further clinical trials using glutamine as a pharmacologic supplement to standard nutrition are warranted.