Isner won the match, and now 14 years on here they both are on Centre Court, competing for a place in the Wimbledon final.
The match set Wimbledon semifinal records for number of games (was 72) as well as duration - the 6 hours, 36 minute match bested the previous mark by 1 hour, 52 minutes.
Surprisingly, it wasn't the longest match in Wimbledon history.
Isner won the longest match at Wimbledon - or any other tournament - when he beat Nicolas Mahut 70-68 in the fifth set after 11 hours, 5 minutes in 2010.
Isner and Raonic entered Wednesday night's quarter-final as the two leading players for aces in the tournament at 135 and 117 respectively. His 53 on Friday gave him 214 for the fortnight, beating the mark of 213 set by Goran Ivanisevic in 2001.
The 32-year-old, the first South African Wimbledon men's finalist since Brian Norton in 1921, faces Novak Djokovic or Rafael Nadal in Sunday's showpiece. Djokovic owns 12 Slam trophies, three from Wimbledon.
Anderson, who graduated from the University of IL, came through another marathon match to beat Roger Federer in the quarterfinals on Wednesday, winning their fifth set 13-11.
With the match tied 13-13, fans howled after a spectator shouted out, "Come on guys, we want to see Rafa!" In his final Collegiate season in 2007, John Isner led his team towards the NCAA Division I Men's Tennis Championship title, defeating the University of Illinois Fighting Illini 4-0 at home in Georgia.
Competing for the University of Georgia Bulldogs between 2003-2007 and he had an awesome result in both singles and doubles, winning 283 matches for the Bulldogs overall!
Besides playing for the Wimbledon title, there was plenty of financial incentive for both players.