Knox, an American college student originally from Seattle, was found guilty of killing her British roommate, Meredith Kercher in 2007. Knox, 22, is currently serving a 26-year sentence in an Italian prison. But her case is still very much in play.
Knox's family is pushing to set her free through the appeals process.
However, their case may have been dealt a deadly blow late last week when prosecutors filed a notice seeking to increase Knox's punishment to life in prison.
In the formal notice to extend her sentence, prosecutors cited Knox's "lack of remorse."
But Edda Mellas, Knox's mother, says that's "ridiculous." Mellas said, "Amanda showed a lot of devastation over the loss of her friend, but you know, you don't apologize for something you didn't do."
Now, Knox's attorneys are firing back, filing their appeal, a 201-page document that attacks her conviction on three key points: her long, initial interrogation by police when Knox says she was forced to confess, what they call the prosecutor's contradictory evidence, as well as what they claim is shaky DNA evidence used to convict her.
Her family says Knox is trying to stay positive.
Mellas told CBS News, "She's hanging in there. It's always better for her when things are moving and it feels like the process is going forward so that she'll get out."
Last month, judges and jurors outlined their reasons for their verdict in the case. They said Knox did not plan the murder of her British roommate Meredith Kercher, but took part in the killing and the cover-up. An appeal could re-open the entire case.
Curt Knox, Amanda's father, told CBS News, "We're looking forward to having that opportunity to take place over there so that she can really be tried, and the evidence really looked at and I think when they do that, they'll find that she's innocent and we'll get to bring her home."
Both sides will now have to present their evidence before an appeals court, essentially, a re-trial of the key evidence in the case.
But could this new push by the prosecution harm Knox's chances of walking free?
Theodore Simon, an American attorney for Knox, said on "The Early Show" Monday the "complete absence of physical evidence," including DNA, will win over a new jury.
"It's absolutely clear that there is no forensic evidence of any sort of Amanda Knox in the room where Meredith Kercher was sadly and tragically killed or on her person. And given the fact this was a violent and terrible murder, one would think that would have to be."
The jurors in Knox's case said they saw the forensic evidence as a key to her conviction. Attorneys for Knox had their request denied to have a third-party review the evidence. Will a second jury think differently?
Simon said, "Many people in the United States have come to believe that conventional DNA testing will convict the guilty and exonerate the innocent, and we believe that, as well. However, most of the public is unaware that the type of testing that was employed in this case was very controversial, and it was an unreliable test known as low-copy number or low-template number. This is not recognized as being truly accepted and reliable and is subject to unreliable results. So we have consulted some of the world's leading experts that would say this and we believe this is simply unreliable testing yielding unreliable results."
However, if Knox doesn't win her appeal, Simon says it's not over for her.
"We're encouraged by this appeal because in Italy, unlike the united states, there's a broader review than there is in the U.S. And not only the legal issues, but the factual issues can be revisited. We're hopeful that this appeal will be recognized as meritorious, but in any event, she has a further appeal to the Supreme Court."
Knox's Italian ex-boyfriend Raffaele Sollecito was also sentenced in Kercher's killing. He got 25 years. Rudy Hermann Guede, an Ivory Coast national, was also convicted of murder in a separate trial. He received a 30-year sentence.