Painting in the Southern Low Countries in the 15th century reflects the economic and cultural prosperity of the region under the dukes of Burgundy. Located first in Bruges and subsequently in Brussels, the court of Burgundy supported the arts in general and painting in particular with the benefits of its prestigious patronage, as illustrated by the Portrait of Anthony of Burgundy by Rogier van der Weyden.

The economic and trading boom of the major cities gave rise to a new, wealthy middle class, which generated both private and official commissions, such as The Justice of Emperor Otto produced by Dirk Bouts for the town hall in Leuven. With this impetus behind them, painters developed a particular attached style that paid great attention to detail and the way the subject matter was presented, as well as their smooth technique and glaze.

Biblical or historical characters, often painted in a domestic setting, were dressed in sumptuous 15th century costumes. The Annunciation by the Master of Flémalle is a good example of this. Alongside the great artists already mentioned, to whom we can add the names of Hans Memling and Petrus Christus, the route offers a selection of paintings attributed to masters with borrowed names (the Master of St. Gudule, the Master of the Legend of St. Lucy etc.) and ends with the room dedicated to Hieronymus Bosch (Triptych of the Temptation of St. Anthony). The Italian school is represented in particular by Carlo Crivelli and the French school by the Master of the Aix Annunciation .