The hospital complex is located a few blocks south of the McCormick Place convention center, overlooking Burnham Park and Lake Michigan.
The old hospital is a low-rise brick building in the classical style. There are several wings and additions, including the two highrise towers.
Adjacent to the hospital grounds is the Prairie Shores residential complex, which was built by directors of Michael Reese Hospital to provide housing for its employees.
Mercy Hospital and its medical center are located in the close vicinity, about three blocks to the northwest.
Michael Reese Hospital has its own stop on the Metra Electric District commuter train line to the east. The station - known as 27th Street-Michael Reese - is only 9 minutes from the Randolph Street Terminal downtown.