North America is experiencing an unprecedented overdose crisis driven by the proliferation of fentanyl and its analogues in the illicit drug supply. In 2018 there were 67,367 drug overdose deaths in the United States, and since 2016, there have been more than 14,700 overdose deaths in Canada, with most related to fentanyl. Despite concerted efforts and some positive progress, current public health, substance use treatment, and harm reduction interventions (such as widespread naloxone distribution and implementation of supervised consumption sites) have not been able to rapidly decrease overdose fatalities. In view of the persistent gaps in services and the limitations of available options, immediate scale-up of low-barrier opioid distribution programs are urgently needed. This includes “off-label” prescription of pharmaceutical grade opioids (e.g., hydromorphone) to disrupt the toxic drug supply and make safer opioids widely available to people at high risk of fatal overdose.