Dexmedetomidine was initially approved for clinical use as a sedative. Its development in pain management has been limited. Dexmedetomidine has analgesic effects and analgesic-sparing properties, especially for patients with obstructed airways. Mixing dexmedetomidine with local anesthetics is a promising new avenue to enhance local anesthetics' effectiveness. Peripheral, spinal and supraspinal α(2A)-ARs are responsible for the analgesic function of dexmedetomidine. Animal studies have shown that antinociceptive synergism results from co-application of dexmedetomidine and opioids or local anesthetics. Dexmedetomidine has potential adverse effects such as hypotension and bradycardia. Therefore, dexmedetomidine is contraindicated for patients suffering from bradycardia or using β-adrenergic antagonists. Clinical trials of dexmedetomidine in chronic pain or hyperalgesia are lack.