Chlorhexidine gluconate (CHG) is a widely used topical antiseptic that is recommended by the Centers for Disease Control and Prevention for skin cleansing before central venous catheter insertion in adults and children. Because of limited safety data, CHG is not recommended for use in children <2 months of age. CHG is, however, frequently used in Neonatal Intensive Care Units across the United States. Here, we will review the safety of CHG use in preterm infants.