In thirteenth-century Siena several lay organizations existed whose members regularly attended masses, participated in religious processions, prayed together and sang hymns or "laude". One kind of confraternities, the "Laudesi" took their name from their custom of singing laude. These were frequently written in honour of the Virgin and Laudesi companies therefore often used a painted image of the Virgin and Christ Child as a focal point of their collective act of singing. The most imposing examples of thirteenth-century Sienese paintings that survive today have been associated with them, including Guido da Siena's panel painting of the Virgin and Christ Child Enthroned, which is the only certain work of the artist.

The picture bears the date 1221. but this has been the subject of much controversy as stylistically the painting seems to belong about half a century later. It has been suggested that the inscription may have some commemorative purpose, the significance of which is now lost, rather than being a record of the date of execution.

Although the painting is majestic in effect and follows Byzantine conventions of iconography, the figures are more natural in posture, to some extent relaxing the stiff linear patterns which had been conventional in central Italian painting up to that time. The throne too is set in a deeper picture space, which adds to the realism of the figures.

On the basis of this picture a number of other panels, most of which are in the Siena Pinacoteca, have been assigned to Guido or his school. Despite his great obscurity, he is regarded as sharing with Coppo di Marcovaldo the honour of founding the Sienese School.