The increase of pronociceptive mediators in the dorsal root ganglia (DRG) and spinal dorsal horn is an important mechanism in the pathogenesis of inflammatory pain and opioid tolerance. Adrenomedullin (AM) belongs to calcitonin gene-related peptide (CGRP) family and has been recently demonstrated to be a pain-related peptide. It has also been shown that the expression and release of AM are increased in the DRG and spinal dorsal horn during inflammation and repeated use of morphine. Intrathecal administration of the selective AM receptor antagonist AM22-52 abolishes inflammatory pain and morphine tolerance, suggesting that enhanced AM receptor signaling in the DRG and spinal dorsal horn contributes to the induction of inflammatory pain and morphine tolerance. The present review highlights the recent developments regarding the involvement of AM in these two disorders. The neurological mechanisms of AM's actions are also discussed.