Identification of pain as the fifth vital sign has resulted in over prescription and overuse of opioids in the United States (US), with addiction reaching epidemic proportions. In Europe, and more recently in the US, a shift has occurred with the global adoption of multimodal analgesia (MMA), which seeks to minimize perioperative opioid use. Improved functional outcomes and reduced healthcare utilization costs have been demonstrated with MMA, but wide scale use of opioids in pain management protocols continues. As a next step in the pain management evolution, opioid-free analgesia (OFA) MMA strategies have emerged as feasible in many surgical settings. Articles were limited to clinical studies and meta-analyses focusing on comparisons between opioid-intensive and opioid-free/opioid-sparing strategies published in English. In this review, elimination or substantial reduction in opioid use with OFA strategies for perioperative acute pain are discussed, with an emphasis on improved pain control and patient satisfaction. Improved functional outcomes and patient recovery, as well as reduced healthcare utilization costs, are also discussed, along with challenges facing the implementation of such strategies. Effective MMA strategies have paved the way for OFA approaches to postoperative pain management, with goals to reduce opioid prescriptions, improve patient recovery, and reduce overall healthcare resource utilization and costs. However, institution-wide deployment and adoption of OFA is still in early stages and will require personalization and better management of patient expectations.