This brief takes the reader on a chemical journey by following the history for over two centuries of how an opiate became an opioid, thus spawning an empire and a series of crises. These imperfect resemblances of alkaloids are both natural and synthetic substances that, particularly in America, are continually part of a growing concern about overuse. This seemed an inviting prospect for those in pain, but as the ubiquitous media coverage continues to lay bare, the levels of abuse point to the fact that perhaps an epidemic is upon us, if not a culture war. Seeking answers to how and why this addiction crisis transpired over two hundred years of long development, this brief examines the role that the chemistry laboratory played in turning patients into consumers. By utilizing a host of diverse sources, this brief seeks to trace the design and the production of opioids and their antecedents.