The gastrointestinal tract is characterized by a self-renewing epithelium fueled by adult stem cells residing at the bottom of the intestinal crypt and gastric glands. Their activity and proliferation is strongly dependent on complex signaling pathways involving other crypt/gland cells as well as surrounding stromal cells. In recent years organoids are becoming increasingly popular as a new and powerful tool to study developmental or other biological processes. Organoids retain morphological and molecular patterns of the tissue they are derived from, are self-organizing, relatively simple to handle and accessible to genetic engineering. This review focuses on the developmental processes and signaling molecules involved in epithelial homeostasis and how a profound knowledge of these mechanisms allowed the establishment of a three dimensional organoid culture derived from adult gastrointestinal stem cells. (C) 2016 Elsevier Inc. All rights reserved.