Portuguese police closed the case in 2008 because authorities had detected no crime. However, a team of detectives from Porto, in northern Portugal, began reviewing the evidence in March 2011. They had not been involved in the original investigation.
The public prosecutor's office in Lisbon said it decided to reopen the investigation after new leads emerged during the case review. It did not elaborate. The case is subject to Portugal's judicial secrecy law, which forbids the release of information about investigations.
British police, meanwhile, launched Operation Grange in 2011 to try to find out what happened to Madeleine. British detectives have been sifting through the case files in Portugal and say they also have identified new avenues of investigation. They say both the timeline and the version of events surrounding the girl's disappearance have changed significantly as new information has emerged.
Madeleine disappeared from her family's resort apartment in Praia da Luz, a coastal town 200 kilometers (120 miles) south of Lisbon, while her parents and their friends were eating dinner nearby.
British detectives say it's possible that Madeleine is still alive.
Ten days ago, British police released a computer-generated image of a person they were interested in questioning about the girl's disappearance. Police asked the public for help and worked with the BBC on a "Crimewatch" TV show, which drew more than 2,000 calls offering possible new leads.
Police said the images were based on information from witnesses who spotted a man in the Portuguese resort the day Madeleine was last seen.
In London, Scotland Yard said the reopened Portuguese investigation will run parallel to the British police's efforts, and British police will be traveling regularly to Portugal.
"Both sides of the investigation are at relatively early stages, with much work remaining to be done," Scotland Yard said in a statement. "This new momentum is encouraging, but we still have a way to go."
Experts say all those efforts are worthwhile.
Even after so many years, officials should "do whatever it takes" to ensure that grieving parents get closure, said Delphine Moralis of Missing Children Europe, an umbrella group of 28 non-governmental organizations in 19 European Union countries and Switzerland.
"It's essential to keep the ball rolling" on efforts to find missing children, Moralis said by telephone from Brussels.
She cited as examples the cathartic resolution provided in the cases involving Natascha Kampusch, who was found eight years after being kidnapped in 1998 in Austria, and three women rescued in May after being held captive in a Cleveland house for about a decade.
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Gregory Katz in London contributed to this report.