Recent advances in neonatology and dermatology have provided us with a better understanding of neonatal and premature infant skin. The problems associated with immature skin become evident immediately after birth and require constant attention throughout the neonatal period. As advances in neonatal care push the gestational age of viability lower, skin maturation and function become increasingly important clinical problems. Premature skin immaturity contributes to elevated water loss, problems with electrolytes and thermoregulation, increased risk of local or systemic infection, increased uptake of potentially toxic agents, and vulnerability to trauma. This review discusses the unique nature of dermal structure and function in very low birth weight infants, evidence of mechanical fragility, toxicity of various topical agents, and the use of emollients. The opinions expressed are those of the authors and do not necessarily represent the views of the Navy or Department of Defense.