The intestinal mucosa has an amazing regenerative capacity, enabling rapid restoration of its physiological functions following injury. The ability to do this resides with the epithelial stem cells located within glandular invaginations in the mucosal surface. Recent advances toward the isolation and characterization of epithelial stem cells has paved the way for exploring novel therapeutic approaches for gastrointestinal disease. Possible stem cell-based therapy of gastrointestinal disorders range from the repair of damaged mucosa through to tissue engineering of artificial intestinal constructs for patients with short bowel syndrome. Before these benefits are realized further information is required on the biological characteristics of intestinal stem cells, their interactions with surrounding cells, and the environment in which they reside. This includes discovering markers to assist in the identification and purification of stem cell populations and techniques to manipulate the cells both in vivo and in vitro. Because intestinal transplantation for patients still represents a significant challenge, it is hoped that one day a tissue-engineered intestine will provide a feasible option for patients with short bowel syndrome. This review aims to introduce the reader to the main characteristics of epithelial stem cells and provide an overview of the current status of intestinal tissue engineering and the problems still being faced.