The focus of this dissertation is the Franciscan church of Santa Caterina (ca.1385-1391) at Galatina in the Salento, an area of Italy characterised by the presence of Greek language and/or rite communities. Scholars have described it as an emblematically ‘Latin’ church, decorated with ‘Giottesque’ frescoes, commissioned by a ruthless and ambitious signore, built with the papacy’s approval, donated to the Franciscan order and founded with the aim of providing mass in Latin for those who did not speak Greek. This dissertation argues that that view needs to be considerably nuanced, if only because the relationship between the Graeci and the Latini in late-medieval Salento is much more complex than often acknowledged. I place Santa Caterina in its context, exploring how the frescoes themselves are evidence for transculturation and how the experience of both communities must be re-centred in order to fully understand the creation and reception of the fresco programme. Before doing this, however, this PhD focuses on the history of the foundation by restoring agency to two of the three main patrons: Raimondello del Balzo Orsini (d.1406) and his wife Maria d'Enghien (d.1446). I argue that the foundation of Santa Caterina was the first sign of Raimondello’s interest in south-eastern Italy, which would allow him to become the first person outside of the royal family to be crowned Prince of Taranto in 1399. I explore the possibility the church may have been built ad instar of St Catherine’s on Mt Sinai, and how this may in turn explain some of its unusual architectural features. This dissertation then takes on the second phase of the church’s history, during which Maria, now Queen of Naples, commissioned the extensive mural decoration. I date the fresco decoration ca.1415-23/5, discuss in detail their iconography, reconstruct lost scenes, and present – for the first time - a holistic interpretation of the mural programme.