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Opioid use has risen dramatically in the past three decades. In the USA, opioid overdose has become a leading cause of unintentional death, surpassing motor vehicle accidents. A patient’s first exposure to opioids may be during the perioperative period, a time where anesthesiologists have a significant role in pain management. Almost all patients in the USA receive opioids during a surgical encounter. Opioids have many undesirable side effects, including potential for misuse, or opioid use disorder. Anesthesiologists and surgeons employ several methods to decrease unnecessary opioid use, opioid-related adverse events, and side effects in the perioperative period. Multimodal analgesia, enhanced recovery pathways, and regional anesthesia are key tools as we work towards optimal opioid stewardship and the ideal of effective analgesia without undesirable sequelae.