Isner, America's highest ranked men's singles player, said he'd like to put himself in the sweepstakes to play mixed doubles with Williams at the London Olympics this summer.
He's not the only one.
Andy Roddick and the Bryan brothers are among those who also have expressed interest in playing with the two-time Olympic gold medalist.
"I may be the odd man out," Isner said on a conference call Tuesday to preview the London Games. "But I'm pretty good friends with Serena. Might need to bribe her, maybe send a gift in the mail to get her to play with me."
Mixed doubles has been added to this year's Olympics, and many players are considering adding doubles and mixed doubles to their schedules, giving them two more ways of bringing home an Olympic medal.
Williams teamed with sister Venus to win the women's doubles gold in 2000 and 2008.
"Obviously, she's one of the most dominant players ever," said Isner, who is ranked ninth in the world. "To have her on my team would be a big advantage."
Earlier this year, Williams said she knew she'd have various options for this year's Olympics, where the tennis tournament will take place at Wimbledon.
"A girl loves to have choices," she said. "Obviously, the Bryans are like the world's best doubles players. Andy and I are super, super close. Personally, I love John. You're not going to break the guy. It's an automatic I don't know how many games. I think it's so hard to choose. I don't know if you just throw everyone's name in a hat and figure out what happens next.
"Regardless, we want to do really well and take home a medal for the country. That's what it's all about."