This chapter explores the current pain management strategies available for one of the most painful procedures: orthopedic fracture surgery. The commonly utilized analgesic modalities are stratified into systemic and regional analgesia. Systemic analgesics, including acetaminophen, NSAIDs, alpha-2 agonists, ketamine, magnesium, gabapentinoids, glucocorticoids, as well as opioids, are discussed in terms of pharmacology, safety, and controversies in use. As for regional anesthesia in fractures, a review of the common peripheral nerve blocks along with their role as part of a multimodal analgesic model is further elaborated with a focus on compartment syndrome and hip fractures. Special patient collectives are also included in the discussion namely pregnant patients, patients with high opioid tolerance such as substance use disorders and chronic pain, along with geriatrics patients. The purpose of the chapter is to investigate the different comprehensive analgesic plans and their respective perioperative outcomes that maximize analgesia, promote mobilization, and minimize potential adverse effects.