Homeostatic epidermal tissue renewal is the result of the combined activity of rare but potent stem cells, and a large pool of short-lived progenitor cells termed transit amplifying cells. Although the existence of epidermal stem cells has been known for some decades, their specific role in the processes of wound repair, skin diseases, and carcinogenesis remains unelucidated. Nevertheless, significant advances have been made in the identification and functional characterization of both murine and human epidermal stem cells, which place investigators in an exciting position to gain further insights into the fundamental processes of tissue renewal and repair in the epidermis.