Sadly, the current opioid crisis is reminiscent of past periods of addiction and overdose deaths in the United States. The crisis today, however, is on a much larger scale owing to how the American appetite for opioids has changed the nature of the drug trade in North America, from the consumption of marijuana and cocaine to that of heroin and fentanyl, and that Mexican transnational criminal organizations have been quick to capitalize on this demand signal at the expense of record levels of drug-related violence and homicides in Mexico. The opioid epidemic is now a health, security, social, economic welfare, and national security crisis. The public, private, and civic sectors must take a more active role in raising awareness of drug abuse and addiction to reduce the demand for opioids, particularly since this opioid epidemic does not discriminate against gender, race, age, economic status, or location. As a transnational crisis, international cooperation to address the supply of illicit opioids is also essential. A whole-of-society approach is required to triumph in the new opium war and overcome this latest opioid epidemic in North America.