Questions regarding the effects of the route of nutrition began to surface shortly after the introduction of total parenteral nutrition (TPN). Although TPN has become a life-saving therapy for patients who cannot tolerate enteral nutrition, it is not the panacea it was hoped to be. It appears that the enteral route of nutrition decreases rates of infectious complications compared with parenteral feeding. Reasons for this phenomenon are not clear, but it seems that enteral nutrition supports the gut barrier and gut-associated lymphoid tissue, which may have effects on infections at distant sites such as the lung. These effects do not appear to be due solely to prevention to malnutrition, as the infectious complications develop early after injury or illness. However, the lack of understanding of the mechanisms does not negate the fact that in many clinical studies the enteral route of nutrition is superior to the parenteral route in terms of reducing infectious complications in critically ill or injured patients.