Two important aspects of the drug epidemic are at the forefront of national attention. The first is the legalization of the production, sale, and use of marijuana. The second is the explosion of drug overdose deaths that has resulted in overdose becoming the leading cause of death for Americans age 50 and younger and has led to a remarkable decline in U.S. life expectancy for the third consecutive year. These are the poles of drug policy: efforts to relax and even eliminate prohibition of marijuana on the one hand and increasing restrictions on opioids to discourage use and to reduce overdose deaths on the other. As we consider present and future drug crises, we can learn useful lessons both from expanding the focus beyond marijuana and opioids and from exploring the path that has led the nation to the current drug epidemic.