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The Virginia Museum of Transportation (VMT) is a museum in Downtown Roanoke, Virginia, that is devoted to the topic of transportation.

Norfolk and Western Railway Freight Station is a historic freight depot located in the Melrose-Rugby neighborhood of Roanoke, Virginia. It encompasses 111 contributing buildings and 2 contributing objects in a planned residential subdivision, with most of the dwellings being built between the late 1910s and late 1940s. It is a primarily residential district with single-family dwellings. The houses include American Craftsman-style bungalow, American Foursquare, and Cape Cod style. The building houses the Virginia Museum of TransportationIt was listed on the National Register of Historic Places in 2013.

Salem Avenue–Roanoke Automotive Commercial Historic District is a national historic district located of Roanoke, Virginia. It encompasses 59 contributing buildings in the southwestern part of the City of Roanoke. The district includes a variety of buildings having automotive, warehouse, light industrial and residential uses. Most of the buildings are small-scale, one or two-story brick or concrete block buildings, with the majority built between about 1920 and 1954. Notable buildings include the former Enfield Buick Dealership (c. 1930), Lindsay-Robinson & Co. Building (1918), Fulton Motor Company Auto Sales & Service (1928), Lacy Edgerton Motor Company (c. 1927), Roanoke Motor Car Company (c. 1946), and Fire Department No. 3 (1909).It was listed on the National Register of Historic Places in 2007, with boundary increases in 2008 and 2014.

Roanoke High School was the first public high school in Roanoke, Virginia. Located at 211-217 Church Ave. S.W., it opened on February 6, 1899. It closed in 1924, replaced by Jefferson High School, and became a school administration building. It was demolished in February 1968 and is now the site of the Noel C. Taylor Municipal Building.

The Robert E. Lee Memorial was a monument commemorating Robert E. Lee, formerly installed in Roanoke, Virginia's Lee Plaza. The stone memorial was approximately 10 feet (3.0 m) tall, and was erected by the United Daughters of the Confederacy in the fall of 1960, just as the first two black students were enrolled in the all-white school system. The monument's erection coincided with the run up to the centennial of the Civil War in 1961. In June 2020, the Roanoke City Council voted to start the legal process to remove the monument and rename Lee Plaza after the July 1, 2020 date when a new state law did away with the prohibition against removing monuments to the Confederate States of America. On just before midnight July 22, 2020, the monument was found to be torn down and broken into two pieces. A 70-year-old man named William Foreman, who was caught vandalizing the monument the night before it was torn down, was arrested on July 24, 2020, and eventually pleaded guilty to a misdemeanor. Lee Plaza was renamed Lacks Plaza after Henrietta Lacks, an African-American woman whose cells are the source of the first immortalized human cell line, and who was born in Roanoke. A statue of Lacks was unveiled in the plaza on October 4, 2023. Evergreen Burial Park submitted a proposal to the Roanoke City Council, to relocate the monument to the burial park that was accepted by the council. The proposed location for the re-erecting the statue is at the east end of the park adjacent to the flagpole dedicated to the Space Shuttle Challenger Disaster.

A statue of Henrietta Lacks was installed in Roanoke, Virginia, in 2024. The artwork was designed by Bryce Cobbs and completed by Lawrence Bechtel.

Roanoke Warehouse Historic District, also known as 'Wholesale Row," is a national historic district located at Roanoke, Virginia. It encompasses five contributing buildings constructed between 1889 and 1902. All the buildings are constructed of brick, two-to-four stories in height and three-to-eleven bays in length. Two of the buildings have exceptional corbeled stepped gables in a Dutch-vernacular tradition. The buildings were erected for wholesale food storage.It was listed on the National Register of Historic Places in 1983.

Campbell Avenue Complex, also known as the Trinkle Buildings, is a historic commercial block and national historic district located at Roanoke, Virginia. It encompasses five contributing buildings constructed between 1892 and 1909. The contiguous three-story buildings are constructed of brick over stone foundations. The buildings have a horizontal arrangement of windows above first-floor storefronts and include buildings representative of the Beaux Arts and Tudor Revival styles.It was listed on the National Register of Historic Places in 1991.

The Roanoke Downtown Historic District is a national historic district located in the Downtown Roanoke area of Roanoke, Virginia. It encompasses 122 contributing buildings. It includes a variety of commercial, institutional, social, and governmental buildings and structures from the late 19th century to the mid-20th century. Notable buildings include the Roanoke City Public Library, the YMCA Central Branch Building, First Christian Church (1925), the Central Church of the Brethren (1924), Tomnes Cawley Funeral Home (1928), Thomas B. Mason Building (1961), Peerless Candy Co. (c. 1916), City Hall / Municipal Building (1915), Roanoke Times Building (1892), Anchor Building / Shenandoah Building (1910), Greene Memorial Methodist Church (1890), and United States Post Office and Courthouse (1930). Located in the district are the separately listed Patrick Henry Hotel, Boxley Building, Campbell Avenue Complex Historic District, Colonial National Bank, and First National Bank.It was listed on the National Register of Historic Places in 2002.

Roanoke station is a train station in Roanoke, Virginia, the current southern terminus of Amtrak's Northeast Regional line. Built in 2017, it follows several other Roanoke passenger stations that operated from the 1850s to 1979. The unstaffed station consists of a single high-level platform with no station building or waiting room available for passengers. All tickets must be purchased in advance; there is no Quik-Trak kiosk at the station.

Carilion Roanoke Memorial Hospital (CRMH) is a private teaching hospital in Roanoke, Virginia, USA. With 703 beds, Carilion Roanoke Memorial Hospital is one of the largest hospitals in the state. It is part of Carilion Clinic.The region's only level I trauma center, the hospital operates three medical helicopters (LifeGuard 10, 11, and 12) to provide air ambulance transport, including one in Moneta, one in Christiansburg, and one in Lexington.

Norfolk and Western Railway Company Historic District is a national historic district located in Roanoke, Virginia. It encompasses three contributing buildings constructed by the Norfolk and Western Railway (N&W). They are the Neoclassical Revival style General Office Building–South (1896, 1903); the Art Deco period General Office Building–North (1931); and the Moderne style Passenger Station (1905, 1949).