Madeleine was three when she disappeared in 2007 from her bedroom while on holiday in Portugal, while her parents, Kate and Gerry, were eating at a nearby tapas restaurant with friends.
Madeleine's disappearance has become one of the most high-profile missing person investigations in history. German police have since declared the case a murder investigation and a person has been named as an official suspect in her disappearance.
Here are the key questions surrounding Madeleine's disappearance and the police investigation that straddled national borders and 15 years.
What are the latest developments?
German national Christian B has been declared an official suspect in the disappearance of Leicestershire toddler Madeleine McCann for the first time in 15 years.
Portuguese authorities haven't formally named him but are acting on request of German authorities.
ITV News has had it confirmed that the formal suspect is Christian B, the man German police first said they were investigating in 2020.
Has he been charged?
No, he has not been charged and denies any involvement in Madeleine’s disappearance.
What did we know about him before?
German media named Christian B, now 44, as a suspect on June 4, 2020.
The convicted German child sex offender is currently in prison in his home country, serving a prison sentence for a sex crime, and has two previous convictions for “sexual contact with girls”.
He lived in the Portuguese coastal village of Praia da Luz on-and-off between 1995 and 2007.
"It's not apparently based on any more evidence" - journalist Natasha Donn tells ITV News naming Christian B as an official suspect is a "stalling move"
Where and when did Madeleine McCann go missing?
The three-year-old disappeared from her room in the family's holiday apartment in the Portuguese village of Praia da Luz on May 3, 2007.
When was she discovered to be missing?
On the night of her disappearance, her parents Kate and Gerry McCann left their three children asleep in their holiday apartment while they went to a nearby tapas restaurant with friends.
The parents and their friends were taking turns to check on the children.
When Mrs McCann checked on them at about 10pm, she found Madeleine missing.
What happened next?
Fears quickly grew Madeleine has been abducted. Sniffer dogs were brought in, the Spanish and border police and airports are notified and volunteers searched the village, beach and resort.
Jane Tanner, one of the friends dining with the McCanns, reports having seen a man carrying a child earlier that night.
Was anyone arrested?
On May 14, detectives took in property developer Robert Murat for questioning and police searched the home he shared with his mother, just 100 yards from where the three-year-old vanished.
He was made an 'arguido', or formal suspect. This was later withdrawn.
In September, during questioning of Mr and Mrs McCann, detectives make them both 'arguidos' in their daughter’s disappearance – but this is also later withdrawn.
What happened to the original investigation by the Portuguese police?
The Portuguese authorities shelved their investigation in 2008 and lifted the 'arguido' status on the McCanns and Robert Murat.
Then, three years later, Scotland Yard opened a review into the case at the request of then-home secretary, Theresa May. The following year, detectives say they believe Madeleine could still be alive and released an age-progression picture of how she might look as a nine-year-old.
London called on the Portuguese authorities to reopen the case, but Portuguese police say they had found no new material.
But, in October 2013, Portuguese police did re-open their case after a review of their original investigation uncovered new lines of inquiry.
What was Scotland Yard’s Operation Grange?
Two years into a review of the case, Scotland Yard launched its own investigation into Madeleine's disappearance. They claimed to have "genuinely new" lines of inquiry and identified 38 people of interest, including 12 Britons.
Operation Grange had received £12.3 million in funding up to April 2020, and remains a missing person inquiry as detectives have no “definitive evidence whether Madeleine is alive or dead”.
Despite a more than £10 million investigation, no one has been charged in connection with Madeleine's disappearance and Scotland Yard's investigation team was reduced from 29 officers to four in 2015.