There are many conditions in the emergency department that require pain management or procedural sedation due to significant pain or complexity. There are also a number of procedures and conditions that will require pain control or anxiolysis in children due to developmental and behavioral factors. Pain control and procedural sedation in pediatric patients can be challenging. A variety of pharmacologic agents can be utilized to minimize anxiety and control pain. These have a wide range of administration routes, including topical, oral, intravenous, intramuscular, intranasal, and regional pain control via nerve blocks. In addition, many non-pharmacologic adjuncts can be coupled with age-appropriate interaction tips to decrease the medications required. This chapter discusses pharmacologic intervention, including narcotic and non-narcotic medications, non-pharmacologic interventions, procedural sedation, and nerve blocks.