Appalachia is loosely defined as areas through which the Appalachian Mountains run, as far south as northern Mississippi and as far north as southern New York. There is some debate about these geographical boundaries, but Appalachia is a useful term when it comes to discussing cultural connections among rural communities throughout the eastern United States. In Dopesick, Macy highlights the ways in which Appalachian culture made rural communities vulnerable to the opioid epidemic and the influence of Appalachian values on responses to the epidemic.

In popular culture, Appalachia is paradoxically both the birthplace of American myths about self-reliance and of poverty as a moral failing. In popular American history, European settlers in places like Kentucky and Virginia are portrayed as hard workers who civilized the wilderness, and their descendants are seen as the laborers responsible for extracting the coal and timber needed to industrialize America. The reality of Appalachia it has always been a diverse place which includes BIPOC residents whose labor and resources contributed to the consolidation and growth of the United States.

While hard work and self-reliance are certainly regional values, the collapse of resource-extraction industries like coal before the Great Depression in the 1930s led to a lack of economic opportunity and dependence on massive government programs to stem poverty and its ill effects.