Hospitalized newborn infants experience pain that can have negative short- and long-term consequences and thus should be prevented and treated. National and international guidelines state that adequate pain management requires valid pain assessment. Nociceptive signals cause a cascade of physical and behavioral reactions that alone or in combination can be observed and used to assess the presence and intensity of pain. Units that are caring for newborn infants must adopt sufficient pain assessment tools to cover the gestational ages and pain types that occurs in their setting. Pain assessment should be performed on a regular basis and any detection of pain should be acted on. Future research should focus on developing and validating pain assessment tools for specific situations.