In 16th century France, Marguerite de Valois is growing up in one of Europe's most dysfunctional families - the Medici clan. Their extreme inbreeding has led to an alarming number of genetic defects in France's kings.

Marguerite alone has escaped this curse. Uncharacteristically beautiful, intelligent, and sane, she is seen as a useful pawn by her mother, Catherine de Medici. In a scheme to unite the country during the raging religious wars, the queen decides to marry her Catholic daughter to Protestant Henri, Prince of Navarre, a charming libertine. De Medici's plan backfires, however, when the populace recoils at the union. Immediately following the wedding a key Huguenot figure is murdered, which leads to the deaths of thousands of Huguenots in Paris, slaughtered by their neighbors in what has come to be known as the St. Bartholomew's Day massacre. Henri barely escapes Paris with his life and Marguerite, sequestered at court by order of de Medici, finds herself a newlywed without a husband.

To make matters worse the Duke of Guise, the powerful man she spurned for Henri, is determined to make her pay for wounding his vanity. In a tale that covers the trajectory of her life, Marguerite, who narrates her own story, comes to understand that to set herself free of the machinations of others, she'll have to outplay them at their own vicious game.