The Italian architect Filippo Brunelleschi began designing the Santo Spirito in the year 1428. After his death, followers of his – Antonio Manetti, Giovanni da Gaiole, and Salvi d'Andrea – carried on his work. The sacristy was designed by Simone del Pollaiolo and the bell tower, built in 1503, was designed by Baccio d'Agnolo.
- The Santo Spirito was only accessible after the Bonfire of the Vanities downloadable content was purchased.
- Despite this, the Santo Spirito was not available in the Assassin's Creed II database, although it was mentioned in the Oltrarno District entry.
- In addition the building was marked with dark grey on the Animus map, same as the landmarks featured in the database.