Knox and Sollecito were tried together and convicted of murder by two separate courts. But now they are free now, forever cleared.
There won't be any civil trials like in the O.J. Simpson case because, according to Italian penal code, Italy's high court decision is final across all courts in the country.
According to Italian lawyer Nicola Canestrini, who works on extradition and criminal cases between Italy and other countries,
What now for the Kerchers?
Francesco Maresca, lawyer for the Kercher family, told CNN that his clients are disappointed with the final ruling.
"We expected more from the Italian judicial system," he said. "This is a failure to find justice for Meredith."
Maresca says the Kerchers could try to appeal to the European Court of Human Rights and argue that Italy failed to find those culpable of killing their beloved daughter and sister but they have yet to make that decision.
"If they think Italy hasn't fulfilled the duty, they could sue Italy," Canestrini told CNN.
Such a claim could be made based on the final conviction handed down to Rudy Guede, a man from the Ivory Coast who was convicted for his role in Kercher's murder in 2008 in a fast-track trial that is still under seal.
When the high court ruled definitively on his case in 2010, they wrote explicitly in their reasoning that he was one of three assailants but did not name who they were.
Knox and Sollecito both spent four years in prison during their initial trial and first appeal. They applied to Italy's high court to be put under house arrest but because Knox was a foreigner and deemed a flight risk, they were both denied.
Sollecito may now have cause to sue Italy for false imprisonment. Italy pays around €12 million every year for locking up people who are later cleared of charges, according to Italian Prime Minister Matteo Renzi who is introduced measures to reform the judicial system.
But, Canestrini says if Sollecito at any time lied to investigators before he was arrested, he may forfeit his right to reimbursement for being held. Sollecito changed his story more than once before finally settling on an alibi with Knox, so a legal battle could focus on whether anything he told investigators led directly to his arrest.
Canestrini also says that Knox could potentially sue Italy for one year of false imprisonment, but because she admittedly lied to investigators early on which led to her arrest, she would likely not have much of a case.
"Because she initially admitted to a role in the crime, she wouldn't likely win. If a suspect lies to investigators before they are arrested, it is difficult to prove they were falsely imprisoned," Canestrini says.
In one of her initial interrogations in 2007, she told investigators she was in the house when Kercher was killed at which time she accused Patrick Lumumba, her boss at a pub where she worked, of the murder.
She later recanted that statement, but Lumumba spent two weeks in prison because of her false claim.
In 2013, Italy's high court ruled definitively on a slander charge against her for the false accusation and upheld a three-year prison term and ordered her to pay Lumumba $40,000 euro.
Knox's lawyer Carlo Dalla Vedova told CNN that Knox doesn't feel any revenge or resentment towards Italy. In fact, he said she will go back one day.
"This has been an nightmare for her, so we finally got the right decision," he said. "We always thought this was the only decision possible."
Sollecito's lawyers were equally pleased with the outcome. "The verdict that we just received doesn't prove us partly right, It proves us completely right," Giulia Bongiorno told reporters outside the court.
"There were two possible verdicts: (One was to) overturn this verdict, but go back to it later. Instead, the overturn is without any referral. Among all the possible and imaginable overturning options, this is the one which says "be advised, we won't ever even make the hypothesis of an implication of Raffaele Sollecito in this case ever. Enough, enough, enough."
Knox, too, made her own statement from her mother's home in Seattle after hearing the news.
She thanked all those who supported her innocence, and said she needed to take time to digest what being free really means.
When asked if she had a message to the Kerchers about their daughter, she said, "She deserved so much in this life. I'm the lucky one."