%0 journal article %@ 0066-4219 %A Stein, C. %D 2016 %J Annual Review of Medicine %N %P 433-451 %R doi:10.1146/annurev-med-062613-093100 %T Opioid Receptors %U https://doi.org/10.1146/annurev-med-062613-093100 %X Opioids are the oldest and most potent drugs for the treatment of severe pain. Their clinical application is undisputed in acute (e.g., postoperative) and cancer pain, but their long-term use in chronic pain has met increasing scrutiny. This article reviews mechanisms underlying opioid analgesia and other opioid actions. It discusses the structure, function, and plasticity of opioid receptors; the central and peripheral sites of analgesic actions and side effects; endogenous and exogenous opioid receptor ligands; and conventional and novel opioid compounds. Challenging clinical situations, such as the tension between chronic pain and addiction, are also illustrated.