Cosimo I created the nucleus of the collection around 1620. It was added to by his son, Ferdinando II, and housed in the first-floor rooms decorated by Pietro da Cortona and by Ciro Ferri.
Cardinal Leopoldo, the brother of Ferdinando II, played a decisive role in enriching the collection, as did Cosimo III and his first-born son, Prince Ferdinando, who bought a number of important Flemish paintings, altarpieces originating from various Tuscan churches together with many outstanding works from the Renaissance and Baroque periods.
Visits now start in the Statue Gallery which houses ancient sculptures from the Villa Medici in Rome, and in the Castagnoli Room.
The adjoining wing, known as Ala del Volterrano, was occupied by the apartments of the Grand Duchesses until the period of Cosimo II; in 1743, Anna Maria Luisa, the last member of the Medici family died there, leaving her huge art collection to the people of Florence.

The works in the Palatine Gallery are laid out in accordance with the aesthetic criteria typical of 17th-century picture galleries. The magnificent carved frames blend in harmoniously with the ornamental motifs of the vault, creating that ideal artistic unity which is at the centre of baroque aesthetics.
In 1915, the Gallery was further extended when the Savoy family donated the entire palace to the State making it possible to double the number of paintings exhibited. Most of the works currently on display originate from the private apartments of the various members of the Medici family.
There are many masterpieces: the Madonna and Child and Episodes from the life of St Anne by Filippo Lippi, dating to around 1450; the Madonna and Child with the Child St John by Raphael (c. 1516) and by the same artist, La Velata; the Child St John by Andrea del Sarto (1523); famous portraits by Titian, Veronese and Tintoretto.