It has long been believed that the thymic epithelial microenvironment originates from both the endodermal and ectodermal germ cell layers. However, a growing body of evidence indicates that such a dual origin is not the case, and that the diverse thymic epithelial populations all develop from a common epithelial stem cell. This article explores these data, investigates the identity of such cells and the signals that might control their expansion and differentiation, and considers the possibility of stem cell transplantation for thymic regeneration.