Epithelial stem cells in the skin are specified during development and are governed by epithelial-mesenchymal interactions to differentially adopt the cell fates that enable them to form the epidermis, hair follicle, and sebaceous gland. In the adult, each of three epithelial lineages maintains their own stem cell population for self-renewal and normal tissue homeostasis. However, in response to injury, at least some of these stem cell niches can be mobilized to repair an epithelial tissue whose resident stem cells have been damaged. How do these stem cell populations respond to multiple signaling networks, activate migration, and proliferation, and differentiate along a specific lineage? Recent clues add new pieces to this multidimensional puzzle. Understanding how these stem cells maintain normal homeostasis and wound repair in the skin is particularly important, as these mechanisms, when defective, lead to skin tissue diseases including cancers.