More than 11 years have passed and she has still not been found. Here's what you need to know.
Little Maddie, then three, disappeared from her bed in a holiday apartment in Rua Dr Agostinho da Silva, Praia da Luz, a resort in the Algarve region of Portugal.
The McCanns arrived on Saturday, April 28, 2007, for a seven-night spring break at the two-bedroom, ground-floor apartment.
It was in the fifth block of a group of apartments known as Waterside Village.
But on the evening of May 3, she vanished from the apartment where she had been sleeping with her brother and sister. Her parents were at a nearby restaurant.
It was due to be the penultimate day of the McCann family holiday.
The three-year-old's disappearance remains one of the most well known missing person cases in British history.
Angela Gallop CBE was the scientist who found vital evidence that solved two of the UK's most notorious murders – Stephen Lawrence and Damilola Taylor.
The forensic biologist, 69, now wants to solve the disappearance of Madeleine, who was three when she vanished from her parents’ holiday apartment in Praia da Luz, Portugal, in 2007.
She told the Sunday Times Magazine: "It would be extraordinarily difficult because it's in a different country and you don't know what's happened to the exhibits.
"I've been involved in cases where it looks hopeless, so I'm not too daunted by anything these days. Every contact leaves a trace, it's just finding it."
The apartment is on the edge of travel firm Mark Warner's Ocean Club resort.
The Ocean Club is one of several tourist sites in the popular holiday town.
It is located close to the larger town of Lagos, about an hour's drive from Faro airport.
In February 2017 the apartment was sold to a British gran for £113,000 – half the asking price.
Police have recorded thousands of potential sightings of missing Maddie since 2007.
Madeleine vanished on May 3, 2007, when her family, from Leicestershire, were holidaying in the Algarve, Portugal.
Parents Gerry and Kate left their three children – including toddler twins Sean and Amelie – sleeping in their apartment while they dined at a nearby tapas bar.
When Kate returned to check on the kids at around 10pm that evening, she discovered that Maddie was not in her bed.
In September of that year Gerry and Kate were named as "arguidos" by Portuguese police.
While arguido is often translated as "suspect", it actually means a person being questioned under caution.
The following summer the McCanns were cleared by investigators in Portugal who declared they had exhausted all avenues in the case.
In 2010, Maddie’s distraught parents met with then-home secretary Theresa May to talk about the hunt for their daughter.
The following year, Scotland Yard launched its own review, named Operation Grange, into the case at the behest of the future PM.
Two years later Scotland Yard said it had uncovered new leads while Portuguese police reopened their case.
In October 2015, Operation Grange was scaled down from 29 detectives to just four.
In December 2016, the Tory government injected extra funding into the operation as cops investigated a new theory that Maddie was snatched by a human trafficking ring.
In October 2017, cops said they were now hunting a "person of significance" in a shock new development.
A source close to Scotland Yard's search Operation Grange said the person is now a "critical line of inquiry" in the £12million investigation.
And a former Met police chief called for a fresh interview of Maddie's parents and the Tapas Seven – who have never been quizzed by British cops.
In November 2017 it emerged a new line of enquiry saw cops travel to Bulgaria to try and track down a paedophile's widow.
In March 2018, Scotland Yard won Home Office funding to continue chasing a vital "final line of enquiry" for a further six months.
Following the conclusion of that six month period, Scotland Yard made a formal request to the Home Office for a further six months of funding.
Maddie turned 15 on May 12, 2018.
In April 2012, UK cops released a computer-generated image of Maddie showing what she would look like aged nine.
A number of potential leads have emerged since the little girl vanished, but none have amounted to anything and no arrests have ever been made.
In January 2019, Maddie's parents were boosted by the news that 13-year-old American schoolgirl Jayme Closs had been found three months after her kidnap.
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