The misuse of prescription medications is a growing problem in Kentucky (Bunn and Slavova 2012). However, the burden of prescription drug abuse is not borne equally throughout the commonwealth. This article will discuss the issue of prescription painkiller misuse and present original research on self-reported use and perception of use to demonstrate the wide disparity between Appalachians and residents of Appalachian counties and statewide averages. The issue of prescription drug misuse in Appalachian Kentucky has been studied, but this study aims to shed light on the breadth of the issue for the general population, not just users. To understand public awareness of opioid overdoses, the 2012 Kentucky Health Issues Poll (KHIP) asked adults in Kentucky about their awareness of the issue, their personal experience with prescription drug misuse, and their indirect experience with the issue. In two out of three measures (awareness and indirect experience), residents of Appalachian counties and adults of Appalachian heritage reported significantly higher percentages of awareness of the problem and friends and family members who misuse prescription pain medicine. Health policy and actions individual readers can take to reduce the risk of painkiller misuse are discussed.