'Lack of evidence'
In legal paperwork published in December 2011, the judge in the case wrote that the jury had cleared the pair of murder for lack of evidence proving they were guilty.
Knox's family said last year the appeal was unwelcome, but no cause for concern.
"The appeal of Amanda's acquittal by the prosecution was not unexpected as they had indicated from the day of the verdict that they would appeal," a family statement in February 2012 said.
Knox has spent the last year and a half trying to resume a normal life, studying creative writing at the University of Washington in Seattle, her hometown, according to family spokesman Marriott.
She also has written a book on her ordeal, titled "Waiting to be Heard," which will be published next month.
According to Harper Collins, Knox "tells the full story of her harrowing ordeal in Italy -- a labyrinthine nightmare of crime and punishment, innocence and vindication -- and of the unwavering support of family and friends who tirelessly worked to help her win her freedom."
The publisher did not have any immediate response to the news that Knox now faces a retrial.
Francesco Sollecito, Raffaele's father, told CNN in a phone interview last year that the family was "not happy about the decision (to appeal). My son is trying to get back to normal life."
"We can do very little in this situation," he said, but as Italian citizens, they would have to accept the court's decision.
"We hope that the high court will finally put the words 'the end' to this story."