Fragments of frescoes were found in the late nineteenth century on the medieval apse wall, hidden behind the fifteenth-century chancel, of the Dominican nunnery church of San Sisto Vecchio, Rome. They were painted in two phases, one in the late thirteenth or early fourteenth century, the other approximately a century later. When they were restored in 1990–2, two new scenes came to light. This paper reconsiders the murals of both phases, including the images uncovered during the restoration campaigns. Historical evidence shines new light on the medieval patrons of the nunnery, who were relatives of individual nuns, and reveals the social context in which buildings and paintings were provided for the convent. It is argued that the frescoes were designed for the Dominican nuns, whose religious ideals are reflected in their iconography. Up until now studies of these murals have not paid much attention to their socio-historical importance, nor the Dominican significance of the images, even in two scenes from the life of Saint Catherine of Siena. Accordingly, this study contributes to the discussion of the frescoes by placing them in a ‘Dominican’ framework, attempting to show what they may have meant to the medieval nuns in the convent.