The US opioid epidemic has changed profoundly in the last 3 years, in ways that require substantial recalibration of the US policy response. This report summarizes the changing nature of overdose deaths in Jefferson County (home to Birmingham, Alabama) using data updated through June 30, 2016. Heroin and fentanyl have come to dominate an escalating epidemic of lethal opioid overdose, whereas opioids commonly obtained by prescription play a minor role, accounting for no more than 15% of reported deaths in 2015. Such local data, along with similar reports from other localities, augment the insights available from the Centers for Disease Control and Prevention's current overdose summary, which lacks data from 2015–2016 and lacks information regarding fentanyl in particular. The observed changes in the opioid epidemic are particularly remarkable because they have emerged despite sustained reductions in opioid prescribing and sustained reductions in prescription opioid misuse. Among US adults, past-year prescription opioid misuse is at its lowest level since 2002. Among 12th graders it is at its lowest level in 20 years. A credible epidemiologic account of the opioid epidemic is as follows: although opioid prescribing by physicians appears to have unleashed the epidemic prior to 2012, physician prescribing no longer plays a major role in sustaining it. The accelerating pace of the opioid epidemic in 2015–2016 requires a serious reconsideration of governmental policy initiatives that continue to focus on reductions in opioid prescribing. The dominant priority should be the assurance of subsidized access to evidence-based medication-assisted treatment for opioid use disorder. Such treatment is lacking across much of the United States at this time. Further aggressive focus on prescription reduction is likely to obtain diminishing returns while creating significant risks for patients.