The Pittsburgh, Cincinnati, Chicago and St. Louis Railroad, commonly called the Pan Handle Route, was a railroad that was part of the Pennsylvania Railroad system. Its common name came from its main line, which began at Pittsburgh, Pennsylvania, crossed the Northern Panhandle of West Virginia, and continued west to Bradford, Ohio, where it split into a northern line to Chicago and a southern one through Indianapolis, Indiana, to East St. Louis, Illinois.

The Pennsylvania Railroad, legal name The Pennsylvania Railroad Company, also known as the "Pennsy", was an American Class I railroad that was established in 1846 and headquartered in Philadelphia. It was named for the commonwealth in which it was established. At its peak in 1882, the Pennsylvania Railroad was the largest railroad, the largest transportation enterprise, and the largest corporation in the world.