In Canada, a rise in opioid use disorder (OUD) and overdose has been linked to opioid prescriptions in a number of contexts. At the same time, relatively few patients prescribed opioids reportedly develop OUD. This combination of findings suggests a pressing need for research on specific avenues through which medically prescribed opioids influence OUD and overdose in Canada. In this commentary, we therefore discuss a few of the potential processes that might allow for medically prescribed opioids to indirectly influence rising overdose rates, and the processes that might account for inconsistencies between large correlational research and studies of OUD incidence in opioid prescribed patients.