This learning activity provides a comprehensive overview of neonatal pain management in the Neonatal Intensive Care Unit (NICU) setting. It explores the paradigm shift in understanding neonatal pain, the short-term and long-term effects of untreated pain, and best practices for assessing and managing pain using nonpharmacologic and pharmacologic interventions. The learning activity emphasizes the importance of implementing evidence-based clinical practice guidelines and quality improvement initiatives, highlighting the critical role of nurses in ensuring consistent, high-quality pain management for these vulnerable patients. It also touches on areas for future research and the ongoing need for education and collaboration among healthcare professionals to optimize neonatal pain management practices, underscoring the ethical imperative to protect these fragile patients from unnecessary suffering and promote their healthy development.