Chronic pain affects an estimated 100 million Americans, or one third of the U.S. population. Approximately 25 million have moderate to severe chronic pain that limits activities and diminishes quality of life. Pain is the primary reason that Americans receive disability insurance, and societal costs are estimated at between $560 billion and $630 billion per year due to missed workdays and medical expenses. Although there are many treatments for chronic pain, an estimated 5 to 8 million Americans use opioids for long-term management. Opioid prescriptions and use have increased dramatically over the past 20 years; the number of opioid prescriptions for pain treatment was 76 million in 1991 but reached 219 million in 2011. This striking increase has paralleled increases in opioid overdoses and treatment for addiction to prescription painkillers. Yet, evidence also indicates that 40% to 70% of persons with chronic pain do not receive proper medical treatment, with concerns for both overtreatment and undertreatment. Together, the prevalence of chronic pain and the increasing use of opioids have created a silent epidemic of distress, disability, and danger to a large percentage of Americans. The overriding question is: Are we, as a nation, approaching management of chronic pain in the best possible manner that maximizes effectiveness and minimizes harm? On 29 and 30 September 2014, the National Institutes of Health (NIH) convened a Pathways to Prevention workshop, The Role of Opioids in the Treatment of Chronic Pain. The workshop involved a panel of 7 experts, featured more than 20 speakers, and was informed by a systematic review conducted by the Pacific Northwest Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality (1). The EPC review addressed evidence about the long-term effectiveness of opioids, the safety and harms of opioids, the effects of different opioid management strategies, and the effectiveness of risk mitigation strategies for opioid treatment. Context The expert panel considered in detail many contextual issues that affect understanding about the dilemma of opioid use and chronic pain (see the full report at https://prevention.nih.gov/programs-events/pathways-to-prevention/workshops/opioids-chronic-pain/workshop-resources#finalreport). Some of these are discussed in the following paragraphs. The burden of dealing with unremitting pain can be devastating to a patient's psychological well-being and can negatively affect their ability to maintain gainful employment or achieve meaningful professional advancement. It can affect relationships with spouses and significant others; may limit engagement with friends and other social activities; and may induce fear, demoralization, anxiety, and depression. Health care providers, who are often poorly trained in the management of chronic pain, are sometimes quick to label patients as drug-seeking or as addicts who overestimate their pain. Some physicians fire patients for increasing their dose or for merely voicing concerns about their pain management. These experiences may make patients feel stigmatized or feel as if others view them as criminals and may heighten fears that their pain-relieving medications will be taken away, leaving them in chronic, disabling pain. Some patients who adhere to their prescriptions may believe that their pain is managed adequately, but others using opioids in the long term may continue to have moderate to severe pain and diminished quality of life. Although many physicians believe that opioid treatment can be valuable for patients, many also believe that patient expectations for pain relief may be unrealistic and that long-term opioid prescribing can complicate and impair their therapeutic alliance with the patient. Although some patients gain substantial pain relief from opioids and do not have adverse effects, these benefits must be weighed against the problems caused by the vast number of opioids now prescribed and the fact that opioids are finding their way illicitly into the public arena. The Substance Abuse and Mental Health Services Administration's 2013 National Survey on Drug Use and Health found that, among persons aged 12 years or older who were abusing analgesics, 53% reported receiving them for free from a friend or relative (2). According to the Centers for Disease Control and Prevention, approximately 17000 overdose deaths involving opioids occurred in 2011 (3). From 2000 to 2010, the number of hospitalizations for addiction to prescription opioids increased more than 4-fold to more than 160000 per year. In 2010, one out of every eight deaths among persons aged 25 to 34 years was opioid-related (4). In a 3-year period (2003 to 2006), more than 9000 children were exposed to opioids. Many historical factors have influenced opioid use. All currently available extended-release opioids have been approved for treatment of chronic pain on the basis of 12-week efficacy studies, although there are safety data for extended-release opioids from studies lasting a year (mostly open-label studies). Many immediate-release opioids came on the market without approval from the U.S. Food and Drug Administration (FDA) for treatment of acute pain, but all received approval in recent years. New opioids that were introduced on the market over the past decade, particularly those with extended-release formulations, were attractive to patients and clinicians, who perceived them as safe and effective despite limited evidence. Physicians have little training in how to manage patients with chronic pain and appropriately prescribe medications for them. Physicians are often unable to distinguish among persons who would use opioids for pain management and not develop problems with misuse, those who would use them for pain management and then become addicted, and those who request a prescription because of a primary substance use disorder. Given these complexities, the panel struggled to strike a balance between the ethical principles of beneficence and doing no harmspecifically, between the clinically indicated prescribing of opioids on one hand and the desire to prevent inappropriate prescription abuse and harmful outcomes on the other. These goals should not be mutually exclusive, and in fact, approaches that attempt to achieve both simultaneously are essential to advance the field of chronic pain management. The panel also grappled with making recommendations in the face of little empirical evidence and eventually formulated advice based on its synthesis of the EPC report (1), workshop presentations that focused on clinical experience, and smaller trials and cohort studies. Clinical Issues Patient Assessment and Triage Chronic pain is a complex clinical issue requiring an individualized, multifaceted approach. It spans a multitude of conditions, with varied causes and presentations. Persons living with chronic pain are often lumped into a single category, and treatment approaches are sometimes generalized without supporting evidence. In addition, although pain is a dynamic phenomenon that waxes and wanes over time, it is often viewed and managed with a static approach. For many reasons, including lack of knowledge, practice settings, resource availability, and reimbursement structure, clinicians are often ill-prepared to diagnose, appropriately assess, treat, and monitor patients with chronic pain. The panel identified several important management issues for clinicians. First, they must recognize that patients' manifestation of and response to pain will vary, with genetic, cultural, and psychosocial factors all contributing to this variation. Clinicians' response to patients with pain may differ because of preconceived notions and biases based on racial, ethnic, and other sociodemographic stereotypes. Treating pain and reducing suffering do not always equate, and patients and clinicians sometimes have disparate ideas about successful outcomes. A more holistic approach to the management of chronic pain that is inclusive of the patients' perspectives and desired outcomes should be the goal. Patients, providers, and advocates all agree that opioids are an effective treatment for chronic pain for a subset of patients and that limiting, disrupting, or denying access to opioids for these patients can be harmful. These patients can be safely monitored by using a structured approach that includes optimization of opioid therapy, management of adverse effects, and follow-up visits at regular intervals. The fact that some patients benefit while others do not, or may in fact be harmed, highlights the challenge of appropriate patient selection. Data are lacking on the accuracy and effectiveness of risk prediction instruments for identifying patients at highest risk for adverse outcomes (such as overdose or development of an opioid use disorder). Yet, the panel heard from a workshop speaker that longitudinal studies have demonstrated risk factors (for example, substance use disorders and comorbid psychiatric illnesses) that are associated with these harmful outcomes, and some studies show that patients who are at high risk are most likely to be prescribed opioids and higher doses of them. Although evidence supporting specific risk assessment tools is insufficient, our consensus was that management of chronic pain should be individualized and should be based on a comprehensive clinical assessment that is conducted with dignity and respect and without value judgments or stigmatization of the patient. The initial evaluation should include an appraisal of pain intensity, functional status, and quality of life, as well as an assessment of known risk factors for potential harm, including history of substance use disorders and current substance use; presence of mood, stress, or anxiety disorders; medical comorbidity; and concurrent use of medications with potential drugdrug interactions. A redesign of the electroni