Harlem Hospital opened in 1887, in a Victorian mansion at East 120th Street and the East River.

The hospital occupied part of its present site on the east side of Lenox Avenue between 136th and 137th streets in 1907, where it opened as a 150-bed facility. The hospital has a long and respected reputation as an educator of African American health professionals. Although African American physicians were not appointed to the medical staff in any significant number until 1927, minority physicians have since come to dominate the medical facility and residency programs. The hospital, which currently has 286 beds, is a member of the New York City Health and Hospitals, and a teaching hospital for Columbia University.

Harlem Hospital Center's Modernization Project will include the renovation of the Martin Luther King Jr. Pavilion and construction of a new pavilion on Lenox Avenue between 136th and 137th Streets. The design for the new pavilion has already received the 2005 Design Award of Honor from the New York Chapter of the American Institute of Architects.

The modernization project will also include the preservation of the WPA murals that are located in two of the buildings to be demolished: the Women's Pavilion and the New Nurses Residence. The murals will be reinstalled in the lobby of the New Patient Pavilion.