The relative importance of neonatal health and neonatal skin care has been highlighted in recent years as infant mortality rates have decreased while death rates during the neonatal period remain unacceptably high in many areas of the world. During the neonatal period, many newborns develop preventable, clinically apparent skin problems, and many more, especially preterm neonates, experience morbidity caused by compromised skin barrier integrity. Several strategies are available for protecting the integrity and promoting the hygiene of the skin and augmenting its function as a barrier to TEWL and heat loss and the entrance of infectious or toxic agents. Research defining optimal applications of many of these strategies, however, and the development of new approaches in skin care is one of the greatest challenges in pediatric dermatology and holds promise for improving neonatal outcome in the future. The ability to modulate epidermal barrier function and integrity relies largely on the topical use of protective materials and substances and manipulation of the external environment. As understanding of epidermal barrier development advances, perhaps pharmacologic manipulation of barrier development, as now practiced for augmentation of neonatal lung maturity, will become a reality. In the meantime, greater awareness among neonatal health care practitioners of state-of-the-art strategies for optimizing skin integrity in neonates is an important step toward improving neonatal health.