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Over the past 150 years the skin's structure and function has been the subject of much investigation by scientists. The stratum corneum (SC), the skin's outermost layer and interface with the outside world is now well recognized as the barrier that prevents unwanted materials from entering, and excessive loss of water from exiting the body. This review summarizes the major advances in our understanding of this formidable membrane. The structure of the SC is outlined as well as techniques to visualize the barrier. The lipid organization and ionic gradients, as well as the metabolic responses and underlying cellular signalling that lead to barrier repair and homeostasis are discussed. Finally, a brief overview of the molecular and genetic factors that determine the development of a competent permeability barrier is provided.