The treatment of pain is a difficult clinical-pharmacologic prob-lem, and prescribers of opioids have been caught between a number of competing forces in their attempt to relieve suffering. These forces include evolving opioid outcome data, regulations, advertising, and potential misinterpretation of recommenda-tions and guidelines. Together with opioid misuse and diversion, an “opioid epidemic” has emerged in multiple countries. In 2014, the United States recorded the highest death rate related to opioids (greater than 9/100,000) since the Centers for Disease Control and Prevention (CDC) began tracking these data. These statistics have prompted the FDA to formulate plans for opioid manufacturers to provide training for all opioid prescribers and the CDC to create the first Opioid Prescribing Guidelines for Pre-scribers caring for patients with chronic pain. The FDA has insti-tuted training programs such as the Transmucosal Immediate Release Fentanyl Risk Evaluation and Mitigation Strategy (TIRF-REMS) program to curb the misuse of these products. More recently, the FDA has worked to educate providers on the risks of extended-release/long-acting (ER/LA) opioids. Better data regarding the effectiveness of opioids ver-sus their adverse effects in the treatment of chronic pain are critically needed. Attempts to link the public health problem of opioid misuse to basic science findings, such as opioid-induced hyperalgesia, must be approached cau-tiously. Nevertheless, it is estimated that the United States, which constitutes 4.6% of the world’s population, consumes approximately 80% of the world’s opioids. In contrast, there are several countries in which the medical use of opioids is prohibited, resulting in unmanaged pain after surgery or trauma and near the end of life.