The negative impacts of the opioid epidemic are substantial and increasing rapidly over time. No part of society—including households, governments, and the private sector—is safe from the devastation brought on by this national crisis. The human toll of the combined misuse of prescription opioids, heroin, fentanyl, and related drugs has reached an unthinkable scale, with deaths soaring to more than 53,000 in 2016. Through this analysis of 2016 data, we estimate the magnitude of the economic and quantifiable societal harms and find the potential benefit of preventing opioid overdoses, deaths, and substance use disorders in 2016 would have exceeded $95 billion dollars—and preliminary data for 2017 predict this estimate will increase. This finding calls for substantial increases in funding at all levels—private and public sectors—to prevent opioid misuse and provide treatment for those affected.The potential benefits of eliminating the epidemic are concentrated in productivity gains from saved lives and reductions in substance use, averted health care costs due to fewer overdoses and other health complications, and lower spending on other services currently addressing the burden of opioids like law enforcement and child/family assistance (see Figure 1). These benefits—including savings to governments and increases in economic returns to households and the private sector (see Figure 2)—would accrue to all of society.