The SEPTA Main Line is the section of the SEPTA Regional Rail system from the Zoo Interlocking in West Philadelphia to Lansdale Station in Lansdale, Pennsylvania. The line is 26.25 miles (42.25 km) long, and serves all 13 SEPTA Regional Rail lines.

The Philadelphia to Harrisburg Main Line is a rail line owned and operated by Amtrak in the U.S. state of Pennsylvania. This is the only electrified Amtrak line in the United States outside of the main line of the Northeast Corridor. The line runs from Philadelphia, where it meets the Northeast Corridor at Zoo Junction at milepost 1.9, west to Harrisburg, where electrification ends. The Main Line is part of the longer Keystone Corridor, which continues west to Pittsburgh along the Norfolk Southern Railway's Pittsburgh Line. This section is sometimes referred to as "Keystone East" and is part of Amtrak's Keystone Service.