Systematic conservation planning is well suited to address the many large-scale biodiversity conservation challenges facing the Appalachian region. However, broad, well-connected landscapes will be required to sustain many of the natural resources important to this area into the future. If these landscapes are to be resilient to impending change, it will likely require an orchestrated and collaborative effort reaching across jurisdictional and political boundaries. The first step in realizing this vision is prioritizing discrete places and actions that hold the greatest promise for the protection of biodiversity. Five conservation design elements covering many critical ecological processes and patterns across the Appalachian Landscape Conservation Cooperative (LCC) geography were identified. These elements include large interconnected regions as well as the broad landscapes that connect them. Small areas that are likely to contain larger ecological significance than their size would suggest were also identified.