But one tale on the Bafta-winning ITV show even had the ever-professional McCall "in tatters".
It was series two, where Maureen, from Liverpool, wanted to track down the mother who had walked out on her as a toddler.
The show's producers discovered that, not only was Maureen's mother dead, she had a half-brother and sister who had also been abandoned. Breaking the news proved almost too much for McCall, whose own mother left when she was aged three, and with whom she had a difficult relationship until her death in 2008.
"I'm going to start crying talking about it," the former Big Brother presenter confesses as she recalls her visit to Maureen's home, while Campbell - himself an adopted child - listens intently.
"Before I even went into her house, I was sitting crying in the car. I had to phone the producer and ask her to come and talk me down in the back of the car," McCall, 46, explains. "It all caved in, but I managed to pull myself together for Maureen. I just related to her on a deep level."
After imparting the news, Maureen and mum-of-three McCall "talked through how some mothers just aren't cut out to be mothers".
"And then [Maureen] came over all protective older sister, like, 'I want to meet [my siblings], they've been through exactly the same thing as me'."
Series four makes for equally emotional viewing.
In episode one, we see a Hampshire-based woman track down the son she gave up for adoption more than 40 years ago, and McCall uses her fluent French (her mother was from the country) to help a Yorkshire nurse find her father in the Alps.
"We were both in pieces doing the voice-over for episode one," says Campbell, who tracked down his birth parents as an adult. "You're trying to go, And then... [breaking into pretend sobs] we found them living in France...'"
"And I'm sitting in the voice-over booth going, 'Hang on, keep it running, keep it running, I want to watch Nicky's bits'," McCall adds.
It must be quite draining filming so many emotional scenes? At the end of each day, Campbell, 53, explains "you go back and you hold your children very tight and you give your wife a big kiss".
Despite their easy rapport, McCall doesn't get to spend much time with her "TV husband" during filming - one presenter meets the person looking for their relative, while the other is with the person who's been tracked down. The hosts text each other about how things are going, and meet up when they are filming a reunion.
"It's like being with the bride and the groom on a wedding day - Nicky getting excited with his side and me getting excited with my side," McCall says. "We see each other at the reunions, but we have to whisper because they're meeting next door. "
Between series, both are kept busy with other projects. But it seems that Long Lost Family holds a particularly special place in their hearts.
"Every story, there's a part of it that I can relate to on some level, every single one - of loss, of love, of wonder, of missing something, of feeling guilty and ashamed," says McCall. "You keep thinking, 'How many different stories can there be?' But there are millions. Everybody has a completely different story."
l Long Lost Family returns to ITV tonight