Individuals who have sustained intestinal failure due to trauma or disease are able to survive through the use of parenteral nutrition (PN). Although home PN (HPN) is a lifesaving therapy, patients may, over the long term, be at risk for liver, bone, and immune dysfunction. A limited number of human studies and a large number of animal studies suggest that there may be a chronic inflammatory condition and additionally a potentially lower T-lymphocyte immune function associated with PN administration. This article will primarily focus on a review of the limited clinical literature that examines the effect of long-term PN on the occurrence of inflammatory mediators in HPN patients, and will discuss the factors that are currently hypothesized to contribute to the potential inflammatory sequelae.