But Knox, 26, who has expressed concern about returning to a country where she spent four years behind bars, was not in court.
Neither was Kercher's family, which said in a statement submitted by their lawyer in court on Monday that they would be following the new trial closely from the United Kingdom.
Knox was convicted in 2009 of murdering Kercher, a 21-year old British exchange student who was found stabbed to death in November 2007 in the villa the two young women rented in the central Italian university town of Perugia.
The convictions of Knox and her ex-boyfriend, Raffaele Sollecito, were overturned in 2011 for "lack of evidence."
After her acquittal, Knox returned to her hometown of Seattle, where she has been living since.
But Italy's Supreme Court decided last year to retry the case, saying the jury that acquitted Knox didn't consider all the evidence, and that discrepancies in testimony needed to be answered.
The retrial's opening day Monday was dominated by procedural items. The presiding judge, Alessandro Nencini, read out the facts of the case, including the conviction of Ivory Coast native Rudy Guede for his role in Kercher's murder.
The defense teams asked for several items of evidence to be retested for DNA, and Nencini agreed that a knife found in Sollecito's apartment would be re-examined. The court also agreed to hear testimony from Luciano Aviello, who served time in jail with Sollecito and claims that his brother killed Kercher.
Also absent from the proceedings Monday was Giuliano Mignini, the Perugia prosecutor who won the original conviction and then lost the appeal.
However, Patrick Lumumba, the Congolese bartender Knox originally accused of Kercher's murder was in court. Lumumba spent several weeks in jail after Knox accused him, and he won a defamation suit against her, for which she was ordered to pay €22,000 ($29,800) for his court costs. Also in the gallery were Perugia residents who attended the original trials.
Court was adjourned until Friday, when Aviello will testify. A verdict is expected by the end of the year.
Afraid to go back
Knox has said she's scared to return to Italy.
"I'm afraid to go back there," she said in an interview with CNN's Chris Cuomo in May. "I don't want to go back into prison."
The high court also said evidence could support prosecutors' initial argument -- that Kercher was killed in a twisted sex game gone wrong.
Knox has said such claims are "a bombardment of falsehood and fantasy."
"No one has ever claimed that I was ever taking part in deviant sexual activity. None of my roommates, none of my friends, none of the people who knew me there. This is simply coming out of the prosecution," she told CNN in May. "I was not strapping on leather and bearing a whip. I have never done that. I have never taken part in an orgy. Ever."
The Supreme Court's decision to send the case back to the appeal court for retrial "may be interpreted by the American authorities as double jeopardy -- twice tried for the same fact or the same case," said Riccardo Montana, a law lecturer at City University in London. "In Italy it's not like this, because this is still the same trial."
Sollecito, Knox's former boyfriend, said he plans to stay in the Dominican Republic with a friend. He said he has no immediate plans to return to Italy.
Watching from afar
If the court convicts her, Knox will be ordered to return to Italy. If she refuses, Italy could request her extradition from the United States. But it's not clear if American authorities would comply.
Knox has said she would be willing to take a lie detector test.
"I'd do anything to prove my innocence," she told CNN affiliate ITV earlier this month. "I don't think that is necessary. But like I said, I'm doing everything to prove my innocence. It's just very sad that's what it has come to."
Knox isn't the only person watching the retrial from afar.
Citing health reasons, Kercher's family said in a statement that they decided not to return to Italy for the beginning of the trial after speaking "at great length."
"It is an extremely stressful time for us all and we desperately want to find truth and justice for Meredith, who was so brutally and unnecessarily taken from us, and so we have decided to support each other in the UK and follow closely here," the statement said.
The family said they would remain in close contact with their lawyer, who was in the courtroom Monday.
"We trust that the evidence will be reviewed and any additional testing requested to be granted so that any unanswered questions can be clarified and the court can clearly decide the next steps in this tragic case," the statement said.
CNN's Jethro Mullen reported and wrote from Hong Kong; Erin McLaughlin reported from London. CNN's Barbie Latza Nadeau reported from Florence.