Three-year-old Madeleine McCann vanished from a Portuguese holiday apartment 13 years ago.
In the intervening years, a huge, costly police operation has taken place across much of Europe.
In the latest development, Scotland Yard has turned its focus upon a German sex offender who is currently in jail. German prosecutors say they are assuming Madeleine is dead and are treating it as a murder inquiry.
Madeleine's parents, Kate and Gerry McCann, feel this is "potentially very significant", said family spokesman Clarence Mitchell.
2007
On 3 May Madeleine, from Rothley, Leicestershire, is on holiday with her family at the Ocean Club in Praia da Luz, Portugal.
- Her parents go for dinner with a group of friends at a restaurant in the complex. Madeleine and her younger brother and sister - twins - stay in the apartment, 100 yards away
- The adults had devised a rota system to check on all their children during the evening
- When it is the turn of Kate McCann, she discovers her daughter, Madeleine, has gone
- Police are called and staff and guests at the complex search for her until daybreak
- Border police and airport staff are put on alert and hundreds of volunteers join efforts to find Madeleine in the following days
On 12 May, 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.
Three days later, British-born Robert Murat is made an official suspect - or "arguido".
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 may not be found alive.
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 the UK 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.
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 - who they believe may have abducted their daughter.
In April, Portuguese police fly to the UK to sit in on interviews conducted by Leicestershire Police of the McCanns' friends they had dinner with on the night Madeleine disappeared - the so-called Tapas Seven.
On 3 May, one year since the disappearance, a tearful Mrs McCann urges people to "pray like mad" for the little girl.
By July Portuguese police say they have submitted their final report on the case. 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 the disappearance.
2009 and 2010
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 now look.
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 McCanns' book, Madeleine, is released in May.
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.
2012
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".
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 in Praia da Luz at about the time Madeleine went missing.
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.
2015-19
In September 2015 the British government disclosed that the investigation had cost more than £10m.
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.
2020
A year later, in June 2020, police reveal that a 43-year-old German prisoner - named by German media as Christian B - has been identified as a suspect. The McCanns thank police, saying: "All we have ever wanted is to find her, uncover the truth and bring those responsible to justice.
"We will never give up hope of finding Madeleine alive, but whatever the outcome may be, we need to know as we need to find peace."
German investigators have classed it as a murder inquiry and say they are assuming that Madeleine is dead.