The adaptation to land from amphibians to amniotes was accompanied by drastic changes of the integument, some of which might be reconstructed by studying the formation of the stratum corneum during embryogenesis. As the first amniotes were reptiles, the present review focuses on past and recent information on the evolution of reptilian epidermis and the stratum corneum. We aim to generalize the discussion on the evolution of the skin in amniotes. Corneous cell envelopes were absent in fish, and first appeared in adult amphibian epidermis. Stem reptiles evolved a multilayered stratum corneum based on a programmed cell death, intensified the production of matrix proteins (e.g., HRPs), corneous cell envelope proteins (e.g., loricrine-like, sciellin-like, and transglutaminase), and complex lipids to limit water loss. Other proteins were later produced in association to the soft or hairy epidermis in therapsids (e.g., involucrin, profilaggrin-filaggrin, trichohyalin, trichocytic keratins), or to the hard keratin of hairs, quills, horns, claws (e.g., tyrosine-rich, glycine-rich, sulphur-rich matrix proteins). In sauropsids special proteins associated to hard keratinization in scales (e.g., scale beta-keratins, cytokeratin associated proteins) or feathers (feather beta-keratins and HRPs) were originated. The temporal deposition of beta-keratin in lepidosaurian reptiles originated a vertical stratified epidermis and an intraepidermal shedding layer. The evolutions of the horny layer in Therapsids (mammals) and Saurospids (reptiles and birds) are discussed. The study of the molecules involved in the dermo-epidermal interactions in reptilian skin and the molecular biology of epidermal proteins are among the most urgent future areas of research in the biology of reptilian skin. J. Exp. Zool. (Mol. Dev. Evol.) 298B:12–41, 2003. © 2003 Wiley-Liss, Inc.