Rates and patterns of transition from opioid analgesic to illicit opioid (ie, heroin) use is of great clinical significance. Exposure to opioid analgesics, and whether use is therapeutic or outside a doctor's orders, may have overlapping yet different patterns of transition to heroin use. Yet, this topic is rarely examined in longitudinal studies. With data from the landmark Monitoring the Future (MTF) study, McCabe and colleagues have now studied the transition from adolescent use of opioid analgesics (both medical and nonmedical) to heroin over a seventeen year follow up for adolescents first recruited from 1975 to 2000. Key findings include an overall association of both nonmedical and medical use of opioid analgesics with transition to heroin use, with particular concerns about early nonmedical use. Of note, more recent cohorts apparently have an increased risk of transition to heroin, suggesting a need for minimizing opioid prescribing and for screening of youth and young adults for prior nonmedical opioid analgesic use before prescribing opioids. New research is also suggested to address such questions as: What is the time course of exposure to the start of heroin use? How does the frequency and dosage of exposure matter? Continued analyses of MTF data, as well as exploration of other data are needed to address these and related compelling issues.