Pennsylvania Route 45 (PA 45) is an 86-mile (138 km) long state highway located in central Pennsylvania. PA 45 is called the Purple Heart Highway.The western terminus of the route is at Pennsylvania Route 453 in the Morris Township near the community of Water Street. The eastern terminus is at Pennsylvania Route 642 west of the small town of Mooresburg.

When Pennsylvania's "traffic routes" were established in 1925, PA 45 was originally signed from Herndon to Easton. The 1928 revision expanded this route westward; PA 45 was signed on two different sections, the connection between them being signed as part of US 120 (later US 122, now PA 405, PA 147, and PA 61). The "middle" section was signed from Water Street to Montandon, between Milton and Northumberland, and the east section from Ashland to Easton.

In 1928, the route was under construction from Indianland to Beersville and completed the following year on the Ashland to Easton section. In 1930, the route was paved from Lehigh Gap to Indianland on the eastern section. In 1934, the eastern terminus was moved from Walnut Street to 13th Street in Easton.

In 1932, a western section of PA 45 was opened from Belsano to US 22 near Sankertown and Cresson. The route replaced US 422 from Belsano to Ebensburg and US 22 from Ebensburg to Cresson when those designations were placed on a straighter route. In 1936, the eastern terminus of the middle section was moved from Montandon to Mausdale. In 1946, the eastern terminus of the western section was truncated from Cresson to Ebensburg. Until 1952, the middle section entered Mooresburg on a different route. In 1951, construction began on a bypass which opened in 1952. In 1955, the eastern terminus in the eastern section was moved from 13th Street to Third Street in Easton.

Until 1961, there was a break between Mausdale and Ashland, that was connected when PA 54 was truncated to Mausdale. Also in 1961, the western section of PA 45 was decommissioned; the piece of PA 45 between Belsano and Nanty Glo became part of an extension of PA 933 and is currently part of PA 271.

In 1962, the route was changed from going into State College via US 322 and then PA 26, to go straight from PA 26 to Boalsburg. In 1966 the eastern section was renumbered as PA 248, leaving the current alignment the only one to hold the designation. The eastern terminus was fixed at its current location, with the road reverting to PA 642 from Mooresburg to Mausdale and to PA 54 south/east of Mausdale.

Pennsylvania Route 45 Truck is a 2-mile (3.2 km) long truck route in Mifflinburg, Union County, Pennsylvania. Narrow streets within the borough are avoided by this designation, and a complicated intersection with Pennsylvania Route 304, which does not contain turning lanes, is bypassed. The route is multiplexed with other highways for its entire length: it begins as a portion of Pennsylvania Route 104 southbound, then it is cosigned with Truck 304, before traveling back northbound along Route 304.

Pennsylvania Route 45 Truck is a 17-mile (27 km) long truck route designed to avoid steep grades and sharp turns along mainline Route 45 in western Huntingdon County, Pennsylvania and to bypass a low clearance under a railroad overpass just south of Spruce Creek. The route is somewhat antiquated, multiplexed entirely with other routes, and significantly longer than the twisty mainline. Traveling mostly in Franklin Township and Warriors Mark Township, the route begins in the west by branching northbound along Pennsylvania Route 453, before continuing west along Pennsylvania Route 550, and travelling south along Pennsylvania Route 350 to meet up with its parent.