The cornified cell envelope (CE) is a highly insoluble structure on the inside of the plasma membrane of terminally differentiated keratinocytes. The cellular and molecular biology of the CE is outlined and new areas of research involving the CE are reviewed focussing on morphological and biochemical connections, the sequential gene expression during terminal differentiation, the interaction of lipids and proteins forming the epidermal barrier, the cysteine-rich pool of proteins in the epidermis as well as the molecular cloning and/or characterization of major components of the CE.