This study, conducted as part of the Monitoring the Future annual surveys, sought to examine the motives for nonmedical use of prescription opioids by adolescents, ie, use without a physician's order. More than 12 000 high school seniors completed the survey between 2002 and 2006. Eight percent of high school seniors reported nonmedical use of prescription opioids in the past year, most commonly to relieve tension, get high, or experiment. However, 45% reported use to relieve physical pain. The prevalence of abuse of other substances was highest among those who reported non–pain relief motives, and lowest among those who did not engage in nonmedical use of prescription opioids. Physician identification of motives for nonmedical use of prescription opioids can help to distinguish individuals who need pain management and those who need a more comprehensive assessment for substance abuse.