Skin and squamous epithelia regulate water and heat homeostasis and constitute our first barrier of protection against pathogens. Cells from the outermost layer of the skin, the cornified envelope (stratum corneum), are constantly being shed, imposing a constant demand for replenishment to maintain homeostasis. Hair follicles and sebaceous glands provide protective hair growth and skin sebum, and continuously undergo cycles of growth and regression. The outstanding ability of the epidermis, hair follicles and sebaceous glands to self-renew relies on a population of adult stem cells that are maintained throughout our life span. In this review we will provide an overview of our current knowledge about epidermal stem cells, and some of the molecular mechanisms that identify them and dictate their behaviour. We will also summarise our view on the possible link between adult epidermal stem cells and cancer stem cells within skin and squamous neoplasias. The potential of epidermal stem cells in regenerative medicine and for designing targeted antitumoral therapies will be discussed.