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Pediatric procedure‐related pain management is often incompletely understood, inadequately addressed, and critical in influencing a child's lifelong relationship with the larger healthcare community. We present a comprehensive review of infiltrative anesthetics, including a comparison of their mechanisms of action and relative safety and efficacy data to help guide clinical selection. We also describe the multimodal utilization of adjunct therapies—in series and in parallel—to support the optimization of pediatric periprocedural pain management, enhance the patient experience, and provide alternatives to sedation medication and general anesthesia. In this second of a two‐part series, we present a comprehensive review of infiltrative anesthetics, including a comparison of their mechanisms of action and relative safety and efficacy data to help guide clinical selection. We also describe the multimodal utilization of adjunct therapies—in series and in parallel—to support the optimization of pediatric periprocedural pain management, enhance the patient experience, and provide alternatives to sedation medication and general anesthesia. [ABSTRACT FROM AUTHOR]