The development and maintenance of the skin are dependent on myriad signaling pathways that regulate a variety of cellular processes. In cutaneous epithelial cells, the Notch cascade plays a central role in ensuring that proliferation and differentiation are coordinated appropriately, a function that it imparts during both ontogeny and homeostasis. Aberrations of the Notch signaling pathway result in severe abnormalities in the epidermis and its appendages and cause functional defects such as perturbed barrier function. In addition, impaired Notch signaling is associated with diseases of the skin such as atopy and cancer. The pathology associated with aberrant cutaneous Notch signaling reflects the complex mechanisms underpinning its function in this tissue and involves both cell-autonomous and nonautonomous mechanisms. This review summarizes our current knowledge of the role of Notch signaling in the skin during health and disease.