Intravenous therapy has played an integral role in the advancement of neonatal care during the last 4 decades. Intravenous access is often needed within minutes of delivery for resuscitation and the administration of IV fluids, medications, blood products, and nutrients. Small premature infants, who once would have died, are now being treated with parenteral nutrition and respiratory support for prolonged periods of time. Multiple and prolonged needs for venous access have obligated the use of various IV access devices. Without the placement of these lifesaving lines, many of the sick and premature neonates in today's neonatal intensive care units would die. If they are to reduce the risks for their smallest patients, nurses who place intravenous or arterial lines in neonates should have a clear understanding of neonatal pathophysiology. This article incorporates unique aspects of neonatal care into a review of the selection of an IV access device and site, monitoring of complications, and problem solving.