Adverse drug reactions are common and associated with substantial economic and human costs. Particularly among older adult populations, preventable adverse drug reactions are often caused by drug-drug interactions. All analgesics have side effect profiles and many have known drug-drug interactions. Opioids are recognized as a necessary option for managing moderate-to-severe pain, yet many opioid side effects can be enhanced by metabolic interactions within the liver, involving other drugs, diseases, or genetics. J Pain Symptom Manage 2012; 44: S4-S14. (C) 2012 U. S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.