Appalachia, as defined in the legislation from which the Appalachian Regional Commission derives its authority, is a 205,000-square-mile region that follows the spine of the Appalachian Mountains from southern New York to northern Mississippi. It includes all of West Virginia and parts of 12 other states: Alabama, Georgia, Kentucky, Maryland, Mississippi, New York, North Carolina, Ohio, Pennsylvania, South Carolina, Tennessee, and Virginia.

About 23.6 million people live in the 420 counties of the Appalachian Region; 42 percent of the Region's population is rural, compared with 20 percent of the national population. The Region's economic fortunes were based in the past mostly on extraction of natural resources and manufacturing. The modern economy of the Region is gradually diversifying, with a heavier emphasis on services and widespread development of tourism, especially in more remote areas where there is no other viable industry. Coal remains an important resource, but it is not a major provider of jobs. Manufacturing is still an economic mainstay but is no longer concentrated in a few major industries.