The mammalian skin mediates the primary interphase between the body and the external environment and provides the first line of defense against pathogens, mechanical trauma, sunlight injuries, and chemical stress. Proper physical, biochemical, and immunological composition of the skin is necessary to maintain its barrier function. Therefore, the skin reflects a complex dynamic organ with high cellular turnover during normal tissue replacement and wound repair. Stem cell reservoirs ensure constant skin renewal. Wnt signaling controls stem cell maintenance and fate decisions in various tissues and also reflects a key pathway in controlling skin development and homeostasis. Disruption of Wnt signaling in the skin causes disorders such as alopecia, chronic inflammatory skin diseases or cancer. This review summarizes the role of Wnt signaling during skin development, homeostasis, and disease.