His son Chuck Pagano, head coach of the Colts, takes on Chargers defensive coordinator and younger brother John Pagano in the prime time matchup.
The two brothers have met eight times before as position coaches or coordinators in the NFL. And the younger Pagano isn't shy about acknowledging his 7-1 record.
"John said he's going to outcoach him," San Diego coach Mike McCoy said, smiling. "He said he's been doing it all his life. So I said, 'OK, let's go.'
"No, I think it's great to see brothers like that being in this profession. There's only so many of us that are able to do this at this level, or have the opportunity to do it. So it's great for a family like that with two great guys. They're both phenomenal football coaches, but they're better people."
Sam plans on attending the game with wife Diana.
It's the first time the Paganos have faced each other since Chuck became the head coach of the Colts last year, and John ascended to the defensive coordinator position for San Diego under Norv Turner's final year with the Chargers in 2012.
"The first thing you think about is the one who's going to lose," Sam said. "We'll get together beforehand and take some photos, have some laughs. But it's serious business for both of them. I'll keep my hands in my pockets and wait for it to be over."
Joked John about his father's allegiances: "He's staying at my house, so he'd better be rooting for me, or he might be at a Holiday Inn somewhere."
Chuck, 53, is seven years older than younger brother John. Both were standout players for their father, who spent 26 seasons as the head football coach at Fairview High School in Boulder, Colo., winning three state titles. Sam Pagano also coached overseas in France, Italy and Germany.
"It was great," Chuck said about growing up as a son of a football coach. "I think there would be a ton of people that would love to have had the opportunity that Johnny and I had growing up in a football family. ... Having the opportunity to hang out as a young boy in a football office, in a football locker room and at practice and grow up that way."
When Chuck was a hard-hitting strong safety for his father in high school, John served as the ball boy. And John was on the sidelines for games when his older brother starred at Wyoming.
John was a decent player as well, earning all-state honors as a linebacker in high school and going on to play at Mesa State.
"All I can say is, as a big brother, when I could, I'd take advantage of the situation and work him over pretty good," Chuck said during a conference call with San Diego-area reporters this week. "I can't do that now. He's a lot bigger than I am now.
"I'm really proud of John and what he's done professionally. And I'm prouder of him as a man, as a father and as a husband. He's just an outstanding human being, and I'm proud to call him my brother."
John Pagano was there to support his older brother during his time of need. Chuck Pagano was diagnosed with acute promyelocytic leukemia in September 2012, taking an indefinite leave of absence from his coaching duties with the Colts for chemotherapy.
He underwent three months of treatment, and in November doctors announced that Chuck's cancer was in remission. He later rejoined the team in December. John flew to Indianapolis to be with his brother on San Diego's bye week during his treatment.
"He spent all day with him," Sam said. "They talked a lot. They watched film. They cried. They prayed. And then he [John] caught a red-eye back home.
"It was really good that he went out and spent the day with Chuck."
John has been with the Chargers since 2002, joining the organization as a defensive quality control coach and working his way up to the defensive coordinator position.
"He's great," San Diego safety Eric Weddle said. "He's extremely smart, passionate and aggressive. He's no-nonsense, but he's still able to communicate, and is open to his players, whether it's on the field or off, letting us express what we see as players and relating it to him.
"I think it's one of the best qualities as a coach to listen to your players and take what we say -- whether you agree with it or not -- at least listen. He's done a great job."
The two brothers usually talk regularly during the week. However, John said the two have not talked leading up to Monday's matchup.
"At the end of the day, it's the Chargers vs. the Colts on Monday Night Football," John said. "It will be good to see him before kickoff and say hello, but when that ball's kicked off, the only thing on my mind is about San Diego winning, and that's the most important thing."