Purpose of Review <p>Effective postoperative pain management remains a critical component of perioperative care, with growing emphasis on opioid-sparing multimodal analgesic strategies. Liposomal bupivacaine, a long-acting formulation of bupivacaine utilizing DepoFoam multivesicular liposome technology, was developed to provide prolonged local anesthetic delivery and improve postoperative analgesia. Since its initial FDA approval, its use has expanded across a broad range of surgical specialties and regional anesthesia techniques. This review examines the pharmacology, clinical efficacy, safety profile, and economic considerations surrounding liposomal bupivacaine use in perioperative practice.</p> Recent Findings <p>Current evidence demonstrates that liposomal bupivacaine may reduce postoperative opioid consumption and improve recovery-related outcomes in select patient populations and procedures; however, its superiority over conventional local anesthetic strategies remains inconsistent. Comparisons with optimized multimodal analgesic regimens, including standard bupivacaine with adjuvants and continuous peripheral nerve catheters, highlight important limitations in demonstrating clinically meaningful benefit. Additionally, the higher acquisition cost necessitates careful consideration of procedure-specific factors, institutional pathways, and patient selection.</p> Summary <p>Ultimately, liposomal bupivacaine should be viewed as a specialized component of multimodal analgesia rather than a universal replacement for existing pain management approaches. Future research should focus on identifying patient populations and surgical settings most likely to derive meaningful clinical and economic benefits.</p>