SummaryThe skin is the largest organ covering the entirety of the body. Its role as a physical barrier to the outside world as well as its endocrinological and immunological functions subject it to continuous internal and external mechanical forces. Thus, mechanotransduction is of the utmost importance for the skin in order to process and leverage mechanical input for its various functions. Piezo1 is a mechanosensitive ion channel that is a primary mediator of mechanotransduction and is highly expressed in the skin. The discovery of Piezo1 earned a Nobel Prize, and has had a profound impact on our understanding of physiology and pathology including paramount contributions in cutaneous biology. This review provides insight into the roles of Piezo1 in the development, physiology and pathology of the skin with a special emphasis on the molecular pathways through which it instigates these various roles. In epidermal homeostasis, Piezo1 mediates cell extrusion in conditions of overcrowding and division in conditions of low cellular density. Piezo1 also aids in orchestrating mechanosensation, DNA protection from mechanical stress and the various components of wound healing. Conversely, Piezo1 is pathologically implicated in melanoma progression, wound healing delay, cutaneous scarring and hair loss. By shedding light on these functions, we aim to unravel the potential diagnostic and therapeutic value Piezo1 might hold in the field of Dermatology.