The proper art-historical title of the painting is The Madonna Standing on Clouds with SS. Sixtus and Barbara. This is one of those titles that begs for reduction, however, so everyone calls it the Sistine Madonna.
The painting—excecuted with oils on canvas—was commissioned in 1512 by Pope Julius II in honor of his late uncle, Pope Sixtus IV. Its destination was the Benedictine basilica San Sisto in Piacenza, a church with which the Rovere family had a long-standing relationship.
There is quite a back-story regarding the model. She is assumed to be Margherita Luti (Italian, ca. 1495-?), the daughter of a Roman baker named Francesco. It's believed that Margherita was Raphael's mistress for the last twelve years of his life, from some point in 1508 until his death in 1520.
Bear in mind that there isn't a paper trail or palimony agreement between Raphael and Margherita. Their relationship seems to have been an open secret, though, and there is evidence—through the artist's paintings—that the couple was extremely comfortable with one another. Margherita sat for at least 10 paintings, six of which were Madonnas. However, it is the last painting, La Fornarina (1520), on which the "mistress" claim hangs. In it, she is nude from the waist up (save for a hat), and sports a ribbon around her left upper arm inscribed with Raphael's name.
La Fornarina underwent restoration in 2000, and naturally had a series of x-rays taken before a course of action could be recommended. Those x-rays revealed that Margherita was originally painted wearing a large, square-cut ruby ring on her left ring finger, and the background was filled with branches of myrtle and quince. These are two extremely significant details. The ring is unusual because it would have been likely to be the wedding or betrothal ring of a very wealthy man's bride or bride-to-be, and both myrtle and quince were sacred to the Greek goddess, Venus; they symbolized love, erotic desire, fertility, and fidelity. These details were hidden for nearly 500 years, hastily painted over—probably by one of his assistants—as (or very shortly after) Raphael died.
Whether or not Margherita was Raphael's mistress, fiance, or secret wife, she was undeniably beautiful and inspired tender handling of her likeness in every painting for which she posed.
The two cherubs at the bottom have frequently been copied alone, without the rest of the Sistine Madonna, since the beginning of the 19th-century. They have been printed on everything from embroidery samplers, to candy tins, to umbrellas, to toilet tissue. There are likely hundreds of thousands of people who recognize them but are unaware of the larger painting from which they came.
The Sistine Madonna hangs in the Gemäldegalerie Alte Meister (Old Masters Gallery) of the Staatliche Kunstsammlungen Dresden ("Dresden State Art Collections") in Germany. The painting has been there since 1752/54, except for the years 1945-55 when it was in the possession of the Soviet Union. Thankfully for Dresden, the Soviets repatriated it fairly quickly as a gesture of goodwill.
Dussler, Leopold. Raphael: A Critical Catalogue of his Pictures,
Wall-Paintings and Tapestries.
London and New York: Phaidon, 1971.
Jimenez, Jill Berk, ed. Dictionary of Artists' Models.
London and Chicago: Fitzroy Dearborn Publishers, 2001.
McMahon, Barbara. "Art sleuth uncovers clue to secret Raphael marriage."
The Guardian. Accessed 19 Jul. 2012.
Ruland, Carl. The Works of Raphael Santi da Urbino.
Windsor Castle: Royal Library, 1876.
Scott, MacDougall. Raphael.
London: George Bell & Sons, 1902.