Background: Major efforts to develop objective measurement tools for neonatal pain assessment have been made. However, the challenge of measuring pain in neonates remains, suggesting that contextual factors (CFs) might alter pain response in neonates. Although the role of CFs is increasingly discussed as crucial for pain assessment, they are not well described in the literature and barely considered in the clinical setting. Aim: To explore the impact of CFs on pain response in preterm infants. Method: Literature search was undertaken considering the period from 1990-2009. Studies reporting about the relation between one or more CFs and pain response in preterm infants during heel stick procedure were considered. Results: 23 studies were included. The studies varied highly related to the design, sample, analysis procedures, and examined variables. Six categories of CFs emerged: Age, pain exposure, health status, therapeutic interventions, behavioral status, and demographic factors, indicating that some of the CFs might have an effect on pain response in preterms. However, none of the CFs was consistently related to pain response as evidenced by contradictory findings. Inconsistency between behavioral and physiological pain response related to CFs further aggravates accurate conclusions. Conclusion: This review indicates a possible influence of some CFs on pain response. However, the results remain inconclusive, which is particularly due to the heterogeneity of the studies. CFs need further investigations in order to get more evidence regarding the magnitude of their effect on pain response. Further evidence has the potential to contribute to achieve another level of measurement of this complex phenomenon.