Dr. Katherine Dudding and Dr. Marliese Nist, both nurse scientists, explore the profound impact of pain and stress on neonates, particularly in the NICU, and the critical role of healthcare providers in mitigating these effects. The discussion highlights the challenges of understanding, assessing, and managing neonatal pain and stress, focusing on how early-life stress and pain can affect long-term cognitive, emotional, and social development, especially for preterm and ill infants. The speakers emphasize the importance of a human-centered approach to care, advocating for intentional, individualized interventions that prioritize the comfort and developmental needs of babies, such as nurturing touch and parental involvement. They discuss the limitations of current stress and pain measurement tools and the need for more nuanced data to improve care. The episode stresses the significance of creating a supportive environment in the NICU, including the integration of neuroprotective practices like two-person care during procedures to reduce stress. Furthermore, the conversation notes the necessity of systemic changes, such as standardized pain protocols, advocacy for better staffing ratios, and ongoing education and research to enhance clinical practices and policies. To learn more about this topic, check out the January/February issue of NANN’s journal, Advances in Neonatal Care (ANC), for a special series on stress and pain in neonates, written by Drs. Dudding and Nist.