Most guidelines on neonatal skin care emphasize issues pertaining to healthy, term infants. Few address the complex task of skin barrier maintenance in preterm, very preterm, and extremely preterm infants. Here, we provide an evidence-based review of the literature on skin care of preterm neonates. Interestingly, the stratum corneum does not fully develop until late in the third trimester, and as such, the barrier function of preterm skin is significantly compromised. Numerous interventions are available to augment the weak skin barrier of neonates. Plastic wraps reduce the incidence of hypothermia while semipermeable and transparent adhesive dressings improve skin quality and decrease the incidence of electrolyte abnormalities. Tub bathing causes less body temperature variability than sponge bathing and can be performed as infrequently as once every four days without increasing bacterial colonization of the skin. Topical emollients, particularly sunflower seed oil, appear to reduce the incidence of skin infections in premature neonates-but only in developing countries. In developed countries, studies indicate that topical petrolatum ointment increases the risk of candidemia and coagulase-negative Staphylococcus infection in the preterm population, perhaps by creating a milieu similar to occlusive dressings. For preterm infants with catheters, povidone-iodine and chlorhexidine are comparably effective at preventing catheter colonization. Further studies are necessary to examine the safety and efficacy of various skin care interventions in premature infants with an emphasis placed on subclassifying the patient population. In the interim, it may be beneficial to develop guidelines based on the current body of evidence.