The interplay of biological and pyschosocial factors explain the unique individual differences in opioid requirements that occur among postoperative patients. Nurses must be familiar with the physiologic mechanisms that influence opioid analgesia. Despite growing evidence that doses of opioid analgesics needed to achieve pain relief vary significantly from patient to patient, standardized dosing regimens continue to drive administration of medications for postoperative pain. In this article, evidence-based literature related to the biologic factors that contribute to differences in responses to opioid medication will be examined. Content will assist the Perioperative Nurse to recognize the pharmacology of opioid analgesics and the scientific basis for differences in the body's ability to metabolize and excrete opioids. These differences include age, gender, genetic predisposition, type of surgical procedure, preexisting pain, and prior or concurrent opioid use. Specific terms are introduced and defined to increase understanding of opioid variability.