Many agents, both pharmacologic and nonpharmacologic, have been studied to alleviate neonatal pain, and the research is extensive. The 2 most commonly studied nonpharmacologic agents studied have been sucrose and nonnutritive sucking (NNS). There is increasing evidence that the synergistic effect of sucrose and NNS is more effective than the effect of sucrose or NNS alone. The purpose of this integrative review of the literature was to determine whether there is a relationship between the synergistic effect of combining sucrose and NNS administered before and during painful procedures, and reducing procedural pain in both preterm and term neonates. This integrative review indicates that the combination of sucrose and NNS is a safe, effective, and clinically significant means of providing procedural pain relief in neonates, both term and preterm.