Gastrointestinal (GI) fistulas allow abnormal diversions of GI contents, digestive juices, water, electrolytes, and nutrients from one hollow viscus to another or to the skin, potentially precipitating a wide variety of pathophysiologic effects. Mortality rates have decreased significantly during the past few decades from as high as 40% to 65% to 5.3% to 21.3% largely as a result of advances in intensive care, nutritional support, antimicrobial therapy, wound care, and operative techniques. The primary causes of death secondary to enterocutaneous fistulas have been, and continue to be, malnutrition, electrolyte imbalances, and sepsis, especially in high-output fistulas, which continue to have a mortality rate of about 35%. Priorities in the management of GI fistulas include restoration of blood volume and correction of fluid, electrolyte, and acid-base imbalances; control of infection and sepsis with appropriate antibiotics and drainage of abscesses; initiation of GI tract rest including secretory inhibition and nasogastric suction; control and collection of fistula drainage with protection of the surrounding skin; and provision of optimal nutrition by total parenteral nutrition (TPN) or enteral nutrition (EN) (or both). The role of nutrition support in the management of enterocutaneous fistulas as either TPN or EN is primarily one of supportive care to prevent malnutrition, thereby obviating further deterioration of an already debilitated patient. It has been shown in several studies that TPN has substantially improved the prognosis of GI fistula patients by increasing the rate of spontaneous closure and improving the nutritional status of patients requiring repeat operations. Moreover, other studies have shown that nutritional support decreases or modifies the composition of the GI tract secretions and is thus considered to have a primary therapeutic role in the management of fistula patients. Finally, if a fistula has not closed within 30 to 40 days, or if it is unlikely to close because of a variety of collateral or compounding pathophysiologic conditions, consideration must be given to operative resection of the fistula while continuing to maintain the previous nutritional and metabolic support. The morbidity and mortality rates in such unfortunate patients remain high despite the many recent advances in surgical and metabolic technology.