Epithelia cover the surfaces and line the cavities of the body. Recent studies have highlighted the existence of multiple stem cell compartments within individual epithelia that exhibit striking plasticity in response to tissue damage, transplantation, or tumor development. New knowledge about the composition of the epithelial niche and the transcription factor networks that maintain cell identity has provided new insights into the extrinsic and intrinsic regulation of stem cell behavior. In addition new in vitro tissue substitutes allow better integration of data from human and mouse models.