Severe malabsorption of fluids and nutrients leads to intestinal failure (IF) where intravenous supplementation of nutrients and fluids is necessary to maintain health and/or growth. Long-term treatment of IF implies the start of intravenous support in the outpatient setting (home parenteral nutrition, HPN). Although HPN has proven lifesaving for many patients for more than four decades this strategy remains associated with complications that compromise the quality of life. Many problems relate to the presence of the venous access device and concern infections or vascular occlusion due to thrombosis. Patient training remains key to prevent these complications. Also metabolic problems may arise that involve liver function or composition or bone mineralization. While intestinal transplantation remains inferior to HPN as alternative treatment strategy in terms of survival, promising developments include the introduction of hormones that promote intestinal adaptation, mixed lipid emulsions that decrease liver problems and catheter lock solutions that prevent infections.