This position paper from the College on Problems of Drug Dependence addresses the issues related to non-medical use and abuse of prescription opioids. A central theme throughout is the need to strike a balance between risk management strategies to prevent and deter prescription opioid abuse and the need for physicians and patients to have appropriate access to opioid pharmaceuticals for the treatment of pain. The epidemiology of prescription opioid use and abuse is reviewed. Non-medical use and abuse of prescription opioids are on the rise in the United States, illicit use of several widely prescribed opioids has increased disproportionately more than illicit use, and the prevalence of prescription opioid abuse appears to be similar to that of heroin and cocaine abuse. There is a paucity of abuse liability testing of prescription opioids, and methods should be developed to fill critical gaps in our knowledge in this area. The role of regulatory agencies in preventing diversion of prescription opioids and identifying potential sources of diversion are discussed. More research is needed to identify those populations most at risk for abusing prescription opioids, and then to develop appropriately targeted prevention programs. Treatment options are discussed; these depend on whether or not an abuser is in pain. Prescription opioid abuse has harmful ramifications for the legitimate and appropriate use of opioids, including stigmatization, opiophobia, and undertreatment of pain. Recommended steps to take include further epidemiological research, laboratory testing of prescription opioids to determine abuse liability, and clinical trials to determine the efficacy of different approaches to the prevention and treatment of prescription opioid abuse.