Filippo Brunelleschi designed the building after receiving the commission from the Silk Guild of Florence (Arte della Seta) in 1419. Ospedale degli Innocenti is considered as a significant example of the early Renaissance architecture in Italy. The hospital features a 9- bay loggia that faces Piazza Santissima Annunziata; the "Arte della Seta" built as well as managed by it. The gild was among the city's wealthiest, and just like most guilds, it accepted the responsibility of philanthropic duties.

Hospital of the Innocents used to be a charitable institution that had the responsibility of the welfare of children who were abandoned. The hospital represented humanistic and social views of Florence city during the early Renaissance. Also, it can explain how investors were using the charitable institutions in Florence as savings banks. Moreover, the hospital still remains as an important site with a statement of care and compassion besides its unpleasant downfalls. Sometimes children were abandoned in a basin situated at the front portico. This basin, however, was removed in the year 1660, and a wheel replaced it for secret refuge. A door used to be there that had a rotating horizontal wheel; it was used to bring a child into the building without their parent being seen by anyone. That allowed people to anonymously leave their children so that the orphanage could care for them. That system remained in operation until 1875, which was when the hospital was closed.

Children were received, wet-nursed then weaned. Also, masters were hired and their job was to teach the boys reading and writing. They taught boys skills according to their capabilities. Girls were regarded as the weaker sex and considered as fragile and most vulnerable. The girls were sent to mistresses to teach them how to cook, sew and other occupations that were expected for women. Also, the hospital provided dowries for these girls, and they could choose to become nuns or get married. An extension was constructed to the south, this was along Via de' Fibbiai. It was meant for women who become nuns and those who didn't marry.

Today, Ospedale degli Innocenti houses a museum of Renaissance art and has works by Domenico Ghirlandaio's Adoration of the Magi, Piero di Cosimo, Sandro Botticelli and Luca della Robbia. The fa├žade of this building consists of 9 semicircular arches that spring from the Composite order columns. The windows, which are semicircular, bring this building down, moving towards the earth, and it's a classical style revival. Also, in the arches spandrels, you will find terracotta roundels that are glazed blue and have reliefs of babies that Andrea Della Robbia designed, suggesting the building's function.

There's a ceramic tondo above each column. They were originally meant by Filippo to be blank concavities; however, around 1490 Andrea was hired to fill them in. Several tondi are original ones, but some of them are 19th-century copies. The well-known insignia of the AAP (American Academy of Pediatrics), headquartered in Itasca, Illinois, is also based on one of these tondi. An emphasis has been put on the building's horizontal because it's longer than it's tall. There's a tabernacle window above each and every semicircular arch. The building shows a clean, clear proportion sense. The column's height equals the intercolumniation width and the arcade width, which makes every bay a cube. Also, the simple proportions of this building reflect a new era, one of secular education plus a sense of great clarity and order. Similarly, the entablature height is half the height of the column, as is proper for the clear-minded society.

Filippo Brunelleschi's design was typically based on late Gothic and Classical Roman, Italian Romanesque architecture. The loggia used to be a famous building type, like the Loggia dei Lanzi (Loggia della Signoria). But, in this instance of the Composite Order, the use of circular columns together with classically correct capitals in conjunction with impost blocks (or dosserets) was novel. This is the same when it comes to the circular arches plus the segmented spherical domes that are behind them.

Also, the architectural elements were articulated in grey stone, then set off against the walls white colour. That motif came to be called serene stone (pietra serena). The proportional logic was also novel, and the columns height wasn't arbitrary. If you draw a horizontal line along the columns tops, a square will be created out of the column height and the distance from a column to the next. That desire for geometric order and regularity was to become a significant element in Renaissance architecture. This is why Brunelleschi is among the leading engineers and architects of the Italian Renaissance.

This Foundling Hospital was built in several phases. The first phase, which was from 1419 to 1427, was under direct supervision of Brunelleschi. Under his supervision, Brunelleschi laid the foundations, raised the main walls, finished off the basement of the building with a cryptoporticus underneath the cloister walks plus the lower section of the front that's facing loggia. The later phases, finished in 1439, added the attic story but omitted the pilasters envisioned by Brunelleschi, expanding the building by adding a bay, specifically to the south in 1430. You can see Robbia's Colored terracotta medallions in the arches spandrels (Infants) put up in the year 1485. Despite the medallions popularity today, they weren't the original Brunelleschi's intentions. If this was up to Brunelleschi, these medallions would have just remained empty. Additionally, the vaulted passageway that can be seen in the bay, positioned to the left side of the loggia, was added later. The hospital wasn't formally opened until 1445 since the loggia was begun before this hospital was started.