This article reviews the clinical issue of poorly controlled postoperative pain and therapeutic approaches to address this common healthcare challenge. Postoperative pain is inadequately managed in over 80% of patients in the US, leading to increased morbidity, functional impairment, delayed recovery, prolonged opioid use, and higher healthcare costs. Acute postoperative pain is a predictive factor for the development of chronic pain. More effective analgesic and anesthetic measures are needed to prevent the progression to persistent pain. Local anesthetics and nonopioid analgesics have shown potential benefits as preventive interventions, but their effectiveness is inconsistent. Conventional opioids remain the standard for acute postoperative pain management, but their narrow therapeutic window and adverse effects limit their optimal dosing. New opioids, such as oliceridine, selectively engage intracellular pathways associated with analgesia, potentially improving the balance between pain control and tolerability. Multimodal analgesia, combining different classes of analgesics, is widely accepted to reduce acute postoperative pain while limiting opioid consumption and adverse effects. However, more research is needed to determine if these approaches improve patient outcomes and prevent the progression to chronic pain.This article reviews the clinical issue of poorly controlled postoperative pain and therapeutic approaches to address this common healthcare challenge. Postoperative pain is inadequately managed in over 80% of patients in the US, leading to increased morbidity, functional impairment, delayed recovery, prolonged opioid use, and higher healthcare costs. Acute postoperative pain is a predictive factor for the development of chronic pain. More effective analgesic and anesthetic measures are needed to prevent the progression to persistent pain. Local anesthetics and nonopioid analgesics have shown potential benefits as preventive interventions, but their effectiveness is inconsistent. Conventional opioids remain the standard for acute postoperative pain management, but their narrow therapeutic window and adverse effects limit their optimal dosing. New opioids, such as oliceridine, selectively engage intracellular pathways associated with analgesia, potentially improving the balance between pain control and tolerability. Multimodal analgesia, combining different classes of analgesics, is widely accepted to reduce acute postoperative pain while limiting opioid consumption and adverse effects. However, more research is needed to determine if these approaches improve patient outcomes and prevent the progression to chronic pain.