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To review the benefits of enteral nutrition in contrast to the inflammatory consequences of administration of parenteral nutrition and enteral deprivation. To present the most recent evidence for the mechanisms of these immunologic changes and discuss potential areas for modification to decrease infectious complications of its administration.There is significant data supporting the early initiation of enteral nutrition in both medical and surgical patients unable to meet their caloric goals via oral intake alone. Despite the preference for enteral nutrition, some patients are unable to utilize their gut for nutritious gain and therefore require parenteral nutrition administration, along with its infectious complications. The mechanisms behind these complications are multifactorial and have yet to be fully elucidated. Recent study utilizing both animal and human models has provided further information regarding parenteral nutrition's deleterious effect on intestinal epithelial barrier function along with the complications associated with enterocyte deprivation.Changes associated with parenteral nutrition administration and enteral deprivation are complex with multiple potential areas for modification to allow for safer administration. Recent discovery of the mechanisms behind these changes present exciting areas for future study as to make parenteral nutrition administration in the enterally deprived patient safer.