en Anesthesiology Review <span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">Dexmedetomidine is a highly selective alpha-2 adrenergic agonist increasingly used off-label as an adjuvant to local anesthetics in neuraxial and peripheral regional anesthesia. Its appeal in postoperative pain management stems from the ability to prolong sensory blockade and analgesia while reducing systemic opioid requirements; however, these benefits are counterbalanced by dose-dependent bradycardia, hypotension, sedation, and, in neuraxial techniques, prolongation of motor block. This narrative review provides a route-specific synthesis of clinically relevant evidence for intrathecal, epidural, and pediatric caudal administration and for contemporary fascial plane and related truncal blocks, including transversus abdominis plane, erector spinae plane, quadratus lumborum, pectoral/interpectoral, pectoserratus, serratus anterior plane, and paravertebral blocks. Randomized trials and meta-analyses generally demonstrate longer time to first rescue analgesia and lower postoperative opioid consumption when dexmedetomidine is added to bupivacaine, ropivacaine, or levobupivacaine. The magnitude and consistency of pain-score improvement are more variable and are influenced by surgical population, local anesthetic regimen, dexmedetomidine dose, block approach, and background multimodal analgesia. Intrathecal doses around 3-5 micrograms and perifascial doses near 0.5-1 microgram/kg are frequently studied, but no universal dose can be recommended across techniques. Mechanistically, spinal alpha-2 receptor activation, inhibition of hyperpolarization-activated cation currents, local effects on neural conduction and vascular uptake, and systemic sympatholysis may all contribute. Current U.S. labeling is for intravenous administration; neuraxial and perineural/perifascial administration remains off-label, and long-term human neurotoxicity data are limited</span></span> dexmedetomidine, local anesthetics, postoperative pain, neuraxial anesthesia, fascial plane block, regional anesthesia 52 63 http://tbsrj.mazums.ac.ir/browse.php?a_code=A-10-3644-2&slc_lang=en&sid=1 Mehdi Hojjati Msp556291@gmail.com 100319475328460032200 100319475328460032200 No Department of Burn Surgery, Faculty of Medicine, University of Mazandaran, Sari, Iran. Samira Sobhani ssobhani1983@gmail.com 100319475328460032201 100319475328460032201 Yes Department of Anesthesiology, Faculty of Medicine, University of Mazandaran, Sari, Iran.