The opioid crisis has devastated the U.S. more than any other country, and the epidemic is getting worse. While opioid prescriptions have decreased by more than 40% from its peak in 2010, unfortunately, opioid-related overdose deaths have not declined but continued to increase. With greater scrutiny on prescription opioids, many users switched to the cheaper and more readily available heroin that drove up heroin-related overdose deaths from 2010 to peak in 2016, being overtaken by the spike in synthetic opioid (mostly fentanyl)-related overdose deaths. The surge in fentanyl-related overdose deaths since 2013 is alarming as fentanyl is more potent and deadly. One thing is certain the opioid crisis is not improving but has become dire with the surge in fentanyl-related overdose deaths. Evidence-based strategies have to be implemented in the U.S. to control this epidemic before it destroys more lives. Other countries, including European countries and Canada, have invested more in harm reduction strategies than the U.S. even though they (especially Europe) do not face anywhere near the level of crisis as the U.S. In the long-run, upstream measures (tackling the social determinants of health) are more effective public health strategies to control the epidemic. In the meantime, however, harm reduction strategies have to be employed to mitigate the harm from addiction and overdose deaths.