The current management of Hirschsprung's disease (HSCR) is still associated with significant long-term morbidities despite on-going refinements in surgical care. Over the course of the past 20 years, significant inroads have been made in our understanding of the development of the enteric nervous system and what factors are responsible for the development of HSCR. This has prompted increased interest in the possibility of using this knowledge to develop new alternative and adjunctive therapies for HSCR. The aim of this review is to provide an overview of the current progress being made toward the development of future therapies to improve the outcome for children with HSCR.