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The challenge of setting the Madonna and Child motif into new compositional arrangements occupied Da Vinci, Michelangelo, and Raphael during the first years of the sixteenth century. Soon the problem was expanded to include not only the little John the Baptist but also Saint Joseph, as in Michelangelo's Doni Tondo; the Madonna and Child with Saint Anne is found in several works bv Leonardo.

As with other works from this period, Raphael has drawn heavily upon the example of the two older Florentine masters, but the ultimate result is nevertheless quite original and characteristically Raphaelesque. In this work Raphael synthesizes elements drawn from Leonardo and Michelangelo and compounds them with a decisively Northern landscape and delicate colourist passages dominated by iridescent tones. The pyramid in which the figures are ideally enclosed is still drawn from models provided by Leonardo, but the relationships between the figures, developed through the glances they exchange and through the serene feelings they communicate, carry the composition onto a calmly descriptive plane. The tone of the painting is thus quite different from the tense and restless art of Leonardo. His unsurpassed descriptive capacity permits Raphael to create an image full of human participation and limpid serenity.