By definition, intestinal failure prevails when oral compensation is no longer feasible and parenteral support is necessary to maintain nutritional equilibrium. In the past, conventional treatment has mainly focused on "making the most of what the short bowel syndrome patient still had" by optimizing remnant intestinal function through dietary interventions, antidiarrheals and antisecretory agents. However, modern treatment options are in the near horizon, and the increased understanding of the mediators for intestinal adaptation will lead to the expansion of the limited treatment armamentarium in short bowel syndrome patients with intestinal failure. The clinical meaningfulness and implications of the observed effects of growth hormone, glutamine, glucagon-like peptide 2 (GLP-2) and the dipeptidyl peptidase-4 degradation resistant analog, teduglutide, is presented in this review and balanced against treatment related adverse events and possible unfavourable effects of long-term, possibly lifelong, treatments.