Health care professionals caring for neonates (birth to 28 days of life) and infants up to 1 year of age have a professional and ethical responsibility to provide safe and effective pain management during painful procedures. Despite 14 years of research reports highlighting that sick infants are exposed to large numbers of painful procedures with minimal or no provision of pain management strategies, and generation of abundant evidence to support effectiveness of pain reduction strategies, insufficient practice changes have been made. As untreated pain in infancy has both immediate and longer-term negative consequences, such as increased sensitivity and responses to subsequent pain, it is imperative that widespread sustained practice changes are made to reduce the burden of pain. This review highlights recent advances within the past 2 to 3 years in pain management of acute procedural pain for neonates and infants, proposes recommendations for future research, and addresses practical implications and challenges for implementing best pain management practices.