Three-year-old Madeleine McCann vanished from a Portuguese holiday apartment in May 2007.
In the intervening years, a huge, costly police operation has taken place across much of Europe.
The most recent Met Police investigation, launched in 2011, has cost more than £11m.
In the latest development, Scotland Yard has turned its focus upon a German sex offender who travelled around Portugal in a camper van.
Madeleine's parents Kate and Gerry McCann previously told the BBC they would do "whatever it takes, for as long as it takes" to find their daughter, who went missing 13 years ago.
2007
On 3 May Madeleine, the eldest of three children from Rothley, Leicestershire, went missing from her family's holiday apartment at the Ocean Club, in Praia da Luz.
Her parents had gone for dinner with a group of friends - who would later become known as the Tapas Seven - at a restaurant 100 yards from the apartment.
Later in the evening, Kate McCann went to check on her three children.
Madeleine was gone.
Police were called and about 60 staff and guests at the complex searched until daybreak for the little girl.
Border police and airport staff were put on alert, and hundreds of volunteers joined efforts to find Madeleine in the days after.
On 12 May, with no trace of her yet found, the McCanns issue a statement saying they "cannot describe the anguish and despair" they are feeling.
Portuguese police say they believe Madeleine was abducted but is still alive and in Portugal.
They have a suspect in mind.
Three days later, British-born Robert Murat is made an official suspect - or "arguido" - following a search of his mother's villa 150 yards from the McCanns' holiday apartment.
On 26 May, police issue a description of a man seen on the night of Madeleine's disappearance "carrying a child or an object that could have been taken as a child"
In June, a Portuguese police chief admits vital forensic clues may have been destroyed as the scene was not protected properly.
In July, British police send sniffer dogs to assist the investigation, and inspections of the McCann's apartment and rental car are conducted.
By August it is 100 days since Madeleine disappeared. Investigating officers publicly acknowledge she could be dead.
Police reject newspaper speculation that Mr and Mrs McCann are being considered as suspects, and the McCanns launch a libel action against Portuguese newspaper Tal & Qual. It had claimed police believe the couple killed their daughter.
The McCanns say they are "deeply hurt" by the allegations.
About a week later, on 6 September, Portuguese police interview Kate McCann for 11 hours as a witness.
The next day, detectives make the couple "arguidos".
Days afterwards, the McCanns return home to Rothley, and Portuguese police play down reports that DNA evidence with a 100% match to Madeleine was found in her parents' hire car.
Prosecutors rule there is "no new evidence" in police files to justify re-questioning Gerry and Kate McCann.
In October, Goncalo Amaral, the detective in charge of the inquiry, who criticised British police in a Portuguese newspaper interview, is removed from the case.
He is replaced by Paulo Rebelo, deputy national director of the Portuguese police.
Gerry McCann releases a personal video in November speaking of his belief that his family was watched by "a predator" in the days before his daughter's disappearance.
2008
On 20 January the McCanns release sketches of a suspect - based on a description by a British holidaymaker of a "creepy man" seen at the resort - they believe may have abducted their daughter.
In March, Mr and Mrs McCann accept £550,000 libel damages and front-page apologies from the UK's Express Newspapers over allegations they were responsible for Madeleine's death.
In April, Portuguese police - who deny leaking details of statements given by the McCanns early in the investigation - fly to the UK to sit in on interviews conducted by Leicestershire Police of the so-called Tapas Seven.
Spanish television broadcasts quotes, including some made by Mrs McCann, supposedly telling officers that Madeleine had been upset the night before she disappeared that her mother had not come to her when she cried.
On 3 May, one year since the disappearance, a tearful Mrs McCann urges people to "pray like mad" for the little girl.
Days later, Alipio Ribeiro, the Portuguese police chief criticised for his handling of the case, resigns.
By July Portuguese police say they have submitted their final report on the case, which the attorney general says "will be the object of careful analysis and consideration".
Weeks later, authorities shelve their investigation and lift the "arguido" status of the McCanns. .
British expat Robert Murat, who is also discounted as a suspect, accepts a £600,000 damages settlement over allegations in 11 UK newspapers that he was involved in Madeleine's disappearance.
Meanwhile Portuguese detective Mr Amaral publishes a book about the case, entitled The Truth of the Lie, in which he alleges that Madeleine died in her family's holiday flat.
2009 and 2010
After the publication of Mr Amaral's book, the McCanns announce in May plans to sue him over comments he made in the media.
On 3 November, a one-minute video message - produced in seven languages - is launched by Britain's Child Exploitation and Online Protection Centre, showing new images of how Madeleine might look more than two years older.
In March 2010, the McCanns criticise the release of previously unseen Portuguese police files to British newspapers
The 2,000-page dossier details dozens of possible sightings of Madeleine since her disappearance.
A month later, in April, Gerry McCann says it is "incredibly frustrating" that police in Portugal and the UK had not been actively looking for his daughter "for a very long time".
In November, the couple sign a publishing deal to write a book about Madeleine's disappearance. They also launch a petition calling for a full review of the case by the UK and Portugal.
2011
The McCann's book, Madeleine, is released in May.
In an open letter published in the Sun newspaper, they ask Prime Minister David Cameron to launch an independent review of all information relating to Madeleine's disappearance.
The next day, he writes to the couple and tells them Home Secretary Theresa May will be in touch to set out "new action" involving the Metropolitan Police.
In September, the McCanns request to be "core participants" in the first part of the Leveson Inquiry into the phone-hacking scandal.
When they give evidence in November, the couple tell the inquiry they were left distraught by press suggestions they were responsible for Madeleine's death.
Their lawyer, David Sherborne, describes the McCanns' treatment by the press as a "national scandal".
2012
In her evidence to the Leveson inquiry in January, Daily Star editor Dawn Neesom says she regrets the paper's coverage of Madeleine's disappearance.
Det Ch Insp Andy Redwood, the detective leading the UK review of Madeleine's disappearance, tells an April broadcast of the BBC's Panorama his team is "seeking to bring closure to the case".
A computer-generated image of what Madeleine might look like aged nine is released, a day before Portuguese authorities say they are not reopening their investigation.
2013
In May, UK detectives reviewing the case say they have identified "a number of persons of interest".
By July, Scotland Yard announces it has "new evidence and new witnesses" in the case and opens a formal investigation. It says it is investigating 38 "persons of interest".
The McCann's £1m libel case against former Portuguese police chief Goncalo Amaral begins in Lisbon in September.
By October, Scotland Yard detectives say they have identified 41 potential suspects.
A BBC Crimewatch appeal features e-fit images of a man seen carrying a blond-haired child of three or four, possibly wearing pyjamas, in Praia da Luz at about the time Madeleine went missing.
It also shows a detailed reconstruction of events on the night she disappeared.
Portuguese police reopen their investigation - to run alongside Scotland Yard's - citing "new lines of inquiry".
2014
In January British detectives fly to Portugal amid claims they are planning to make arrests.
In June searches in Praia da Luz are carried out, including an area of scrubland situated south-west of the Ocean Club complex, where the McCann family stayed in 2007. It yields nothing of interest.
A month later, in July, four suspects are quizzed by police but no new developments emerge.
In December detectives interview a further 11 people, although they are not treated as suspects.
2015 onwards
In September 2015 the British government disclosed that the investigation had cost more than £10m.
In February 2017 Portugal's Supreme Court dismissed the long-running libel case against Goncalo Amaral, former head of the local police investigation.
It ruled that his book, which alleged the McCanns disposed of Madeleine's body, was protected by freedom of expression laws.
In April 2017 the four official suspects investigated by police were ruled out of the investigation but senior officers said they were pursuing a "significant line of inquiry".
An extra £150,000 is granted to continue the investigation in November 2018.
It is the latest in a series of six-month extensions which take the cost of Operation Grange to an estimated £11.75m.
In March 2019 Netflix screens an eight-part documentary about Madeleine's disappearance.
Her parents, who did not participate in the film, feel it could "potentially hinder" the police investigation.
In June, the UK government says it will fund the Met Police inquiry, which began in 2011, until March 2020.
A year later, in June 2020, police reveal that a 43-year-old German prisoner has been identified as a suspect in Madeleine's disappearance.
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