Purpose of review <p>Effective postoperative pain management is paramount in spine surgery, where patients often experience severe and prolonged pain related to extensive tissue disruption and long operative times. </p> Recent findings <p>Traditional approaches rely heavily on short-acting opioids, which require frequent dosing and are associated with numerous adverse effects. Intra-operative intravenous methadone has emerged as a favorable alternative related to long duration of action and multimodal mechanism of action. As both a potent µ-opioid receptor agonist and NMDA receptor antagonist, methadone targets multiple pain pathways, offering prolonged pain relief and potential benefits in minimizing central sensitization. The present investigation evaluates current evidence surrounding intra-operative IV methadone in spine surgery. Studies show that methadone reduces postoperative opioid consumption, improves pain scores, and enhances patient satisfaction without significantly increasing adverse events.</p> Summary <p>Despite these advantages, methadone presents important risks, including delayed respiratory depression and QTc interval prolongation, particularly in opioid-naive or medically complex patients. Variability in dosing effects and exclusion of high-risk populations in clinical trials limit our current understanding. In this regard, careful patient selection, preoperative screening, and postoperative monitoring are essential for safe use. Future research should aim to refine dosing protocols and evaluate methadone mediated roles within standardized Enhanced Recovery After Surgery (ERAS) pathways. In summary, intra-operative IV methadone represents a valuable tool in spine surgery analgesia, offering durable pain relief and opioid-sparing effects. With appropriate clinical considerations, it may be an effective component of perioperative spine surgery pain management strategies.</p>