Stem cells have essential functions in the development and maintenance of our organs. Improper regulation of adult stem cells and tissue homeostasis can result in cancers and agedependent decline. Therefore, understanding how tissue specific stem cells can accurately renew tissues is an important aim of regenerative medicine. The Drosophila midgut harbors multipotent adult stem cells that are essential to renew the gut in homeostatic conditions and upon stress-induced regeneration. It is now a widely used model system to decipher regulatory mechanisms of stem cell biology. Here we review recent findings on how adult intestinal stem cells differentiate, interact with their environment, and change during aging.