Stem cells play a key role in tissue homeostasis and renewal after damage, so learning more about them may become a sort of 'Pandora's box', which when opened will make it possible to clarify the nature and the pathophysiology of several human diseases and to find new treatments for pathologies, such as cancers, degenerative, autoimmune and genetic disorders, that are currently untreatable. The characteristics of the gastrointestinal tract and of the liver, in terms of genesis and regeneration and their special relationship with the haemolymphopoietic system, allow stem cell research to outline interesting therapeutic perspectives in these fields. We aim to summarize the knowledge acquired on gastrointestinal and hepatic stem cell biology, focusing attention on the issues that remain to be addressed, and to present the main perspectives of treatment offered by these 'new tools' in gastroenterology and hepatology.