The United States Marine Hospital of Louisville, in the Portland neighborhood was built in 1845, and is considered the best remaining antebellum hospital in the United States. Of the seven hospitals built in the mid-19th century by the Marine Hospital Service "for the benefit of sick seamen, boatmen, and other navigators on the western rivers and lakes." It is the only one still standing, even after surviving two tornadoes. The building has been extensively restored to match its appearance in 1899.
In 2003, the National Trust for Historic Preservation (NTHP) placed the building on its America's Most Endangered Places list, which helped spark public interest in restoring it. The hospital has now been returned to its 1899 appearance, the earliest reference of the building's appearance that can be found. In 2003, the hospital received a $375,000 Save America's Treasures grant from the NTHP to repair its roof and exterior. On November 11, 2005, rebuilding of the structure began. The smokestack, constructed in 1933, was demolished to help return the structure to its 1899 appearance. The octagonal cupola, which patients used to better view the passing river traffic during its heyday, was also rebuilt.