The frequency of painful procedures performed on preterm infants in the neonatal intensive care unit (NICU) presents a challenge to nurses who are attempting to provide effective pain relief, and to the infants themselves who may suffer adverse consequences in response to repeated painful procedures. One new pain relief intervention under study is the administration of oral sucrose, which may activate endogenous opioid systems within the body. Studies with preterm infants that have examined the use of oral sucrose as an analgesic during heelsticks and venipunctures have shown that sucrose is effective in reducing pain. Sucrose may also be combined with nonnutritive sucking to provide significant pain relief. The use of oral sucrose is now recommended with a wide range of painful procedures in the NICU. Promising results have been observed in studies with both term and preterm infants, but less research has occurred with preterm infants. Additional research is warranted to determine the most effective approaches for the administration of sucrose, to examine the effectiveness of sucrose with additional types of painful procedures, and to examine the effects of long-term repeated use of sucrose.