Ghirlandajo was summoned soon to Rome to paint in the Sistine Chapel, afterwards to be so glorious; but his greatest works were done in the prime of his manhood, in his native city, Florence, where he was chosen as the teacher of Michael Angelo, who was apprenticed to Ghirlandajo for three years.
While still in the flower of his age and crowned with golden opinions, being, it is said with effusion, 'the delight of his city,' Ghirlandajo died after a short illness, in Ghirlandajo's time Florence had reached her meridian, and her citizens outvied each other in the magnificence of their gifts to their fair mother city. Ghirlandajo was fitted to be their painter; himself a generous-spirited artist, in the exuberance of life and power, he wished that his fellow-citizens would give him all the walls of the city to cover with frescoes. He was content with the specified sum for his painting, desiring more the approbation of his employers than additional crowns. His genius lying largely in the direction of portrait painting, he introduced frequently the portraits of contemporaries, causing them to figure as spectators of his sacred scenes. One of these contemporaries thus presented, was Amerigo Vespucci, who was to give his name to a continent. Another was a Florentine beauty, a woman of rank, Ginevra de Benci.
Ghirlandajo was lavish in his employment of rich Florentine costumes and architecture. He even made the legends of the saints and the histories of the Bible appear as if they had happened under the shadow of Brunelleschi's duomo and Giotto's campanile, and within sound of the flow of the Arno. In the peculiar colouring used in fresco painting Ghirlandajo excelled.
He painted a chapel for a Florentine citizen, Francesco Sasetti, in the church of the Trinità, Florence, with scenes from the life of St Francis. Of these, the death of St Francis, surrounded by the sorrowing monks of his order, with the figures of Francesco Sasetti and his wife, Madonna Nera, on one side of the picture, is considered the best. As a curious illustration of the modernizing practice of Ghirlandajo, he has painted an old priest at the foot of the bier, chanting the litanies for the dying, with spectacles on his nose, the earliest known representation of these useful instruments.