Painted in the early 1500's (some say 1503, others 1516, with a few other dates thrown about) by Leonard Da Vinci, the Mona Lisa is thought to be the portrait of Lisa del Giocondo, wife of Francesco del Giocondo. However, the painting never made it to the family. Rather, Leonardo liked it so much he kept it, using it as a piece of propaganda in his travels, as a way to show potential clients what he could do.
King Francois I bought the painting from Leonardo's assistant after his master's death, and hung it at Fontainebleau. Courtiers marveled at it. Contemporary sources were talking about the lady's mysterious smile even at this point. Mona Lisa was already becoming quite famous. in the 1600's, the Duke of Buckingham attempted to buy the painting. However, the King of France was begged by his subjects to not sell France's most valuable treasure. The Mona Lisa survived the Revolution and even had a short stay in Napoleon's bedroom before becoming a permanent fixture at the Louvre.
The Mona Lisa was quite revolutionary for its time. The use of light, color, and detail are unprecedented. Many paintings up until this point were colored drawings. Leonardo, however, perfected the sfumanto method of painting. There are no harsh outlines as before, but full strokes of paint, blended together to enhance light and color. Leonardo's paint strokes appear to be "invisible." Some researchers say he used a magnifying glass and painted strokes smaller than a pin head. Others say he layered paint upon paint, taking days to finish tiny sections of the painting.
Despite many today asking why the Mona Lisa is so famous, as it doesn't appear to be revolutionary, one must keep in mind that, in fact, it is. Louvre Curator Jean-Pierre Cuzin stated that, "The entire history of portraiture afterwards depends on the Mona Lisa. If you look at all the other portrait - not only of the Italian Renaissance, but also of the seventeenth to nineteenth centuries...all of them were inspired by this painting. Thus, it is sort of the root, almost, of occidental portrait painting."
References from: The Mona Lisa: History's Most Famous Painting by Donald Sassoon.