Some 16 million children living in the remote and dangerous border areas of Afghanistan and Pakistan are set to be vaccinated for polio this week.
The WHO's aim is for the global eradication of polio
Tens of thousands of health workers will fan out across the region in the coming days to carry out the programme.
It will be one of the most demanding immunisation programmes ever carried out by the World Health Organisation.
But the WHO hopes it will mean the total eradication of polio in Pakistan and Afghanistan.
This would mean polio remained endemic in only two countries, India and Nigeria.
The week-long campaign will target 14 million Pakistani children and two million Afghan children, WHO spokeswoman Fadela Chaib said earlier in the week.
"The virus is still circulating in this corridor, so it's important to target the children who live on the border between the two countries," she told journalists.
This year alone, five cases had been reported in Afghanistan and two in Pakistan, the WHO said.
The organisation's Oliver Rosenbauer told the BBC that the teams would be operating in an area that is not only geographically difficult, but also dangerously insecure.
"It is extremely challenging to run immunisation campaigns in these areas, extremely dangerous," he said.
"We have staff regularly put at risk, staff who are kidnapped. So it's absolutely admirable what they're able to achieve under these circumstances."
The WHO launched a worldwide campaign in 1988 to try and eradicate the virus, but failed in its bid to wipe out polio infections by 2005.
The programme suffered a setback two years ago when northern Nigeria suspended immunisation and the virus spread re-infecting once polio-free countries.
Now the WHO believes the campaign is back on track, and the prize of global eradication is within reach, the BBC's Imogen Foulkes in Geneva reports.