Their first meeting came more than a decade ago in Miami.
Switzerland's elfin Roger Federer, lean -- almost frail to the naked eye -- and wearing a six-inch ponytail and a too-wide white Nike headband, was 22. Five years younger, Rafael Nadal, an absurdly muscular Spaniard, was garbed in his pirate gear of the day.
Federer had just won Indian Wells, defeating Tim Henman in the final, and was the world's No. 1-ranked player. He had also suffered some California sunstroke; after several days in bed, he arrived in Miami.
It wasn't close. On the final point, in a pattern that would be repeated again and again over the years, Nadal hit three successive left-handed forehands to Federer's right-handed backhand. The last led to a thundering overhead -- followed by a joyous knee-lifting, upper-cutting fist pump -- and a startling 6-3, 6-3 victory.
"I don't even remember what the score was exactly," Federer said back in March at this year's Sony Open, his best guess (6-3, 6-4 maybe?) missing the mark by a single game. "I never really got into the match. He played great, and I was impressed with what I saw. I mean, that was clearly for him a big arrival on the scene, because that's always a big deal if you can beat a world No. 1 on hard courts.
"I think everybody thought he was just a clay-courter, and he proved that he was probably going to be more than just that. [He] went on to have this great career many expected him to have."
And so the game, the fascinating elite arms race in men's tennis, was on.
Federer is considered by many to be the greatest player of all time, but he's lost 23 of 33 matches to Nadal.
For now, Federer is the all-time leader with 17 Grand Slam singles titles; Nadal is third, with 13.
They have met five times at the French Open, which begins Sunday in Paris, and Nadal has won all of those fascinating red-clay encounters. How would those major totals be different if Federer had managed to win one or two?
"I don't think you can crystal ball that," said Darren Cahill, former coach of Andre Agassi and Lleyton Hewitt and now an ESPN analyst. "There are so many factors: length of career, luck of the draw, the other players coming through. You've got guys like Novak Djokovic and Andy Murray and now [Stanislas] Wawrinka who think they have a chance to win when they walk out there.
"How many weeks did Roger spend at No. 1? How many consecutive Grand Slam semifinals did he make? You could write a line down the middle of a chalkboard and write all the accolades and achievements of each guy and you'd run out of space."
In the liquid, ever-shifting dynamic between two Grand Slam champions over their careers, each match at a major is charged with historic significance. Pete Sampras and Agassi had nine Grand Slam meetings. Sampras won six of those and five times went on to win the title -- a large part of the reason Sampras finished with 14 Grand Slam singles titles, seven more than Agassi.
Nadal is 9-2 against Federer in Slams, including eight finals. Incredibly, each of those nine wins was a piece of a major championship. If Federer had won two or three of his 0-for-8 run at the Australian Open and Roland Garros, he might own an insurmountable lead as he moves toward retirement.