A rematch of previous year's finals at Roland Garros, it was a gruelling five-setter match.
The pair have only met twice at Wimbledon, Nadal winning their 2007 semi-final when Djokovic retired hurt, the Serb gaining revenge in the 2011 final.
Through five wins in London, the 31-year-old has dropped just two sets and has wrapped up every match in less than three hours. "That's a big thing".
"It is always a big challenge facing Novak".
"He is one of the more complex players that I ever saw on our sport". Sometimes you play your best tennis and it's not enough to beat him. "The goal is to come back next year".
"You have to accept that if you want to win important things. In some ways he deserves to go through too", Nadal told the BBC after the match.
"Friday is another important match against opponent that is one of the most hard ones that you can face".
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A big-serving match tends to have shorter points than one featuring at least one return-orientated player, and so it proved in these - Anderson and Federer played 67 games in 257 minutes (3.84 minutes per game), while it took Nadal and Del Potro 292 minutes to play 55 games (5.31 minutes per game).
This is the longest three-set match in the history as it lasted for four hours and three minutes.
After seven weeks out with a serious knee injury, many doubted if Nadal would regain his crown as the "King of Clay". Of course, have been an emotional match.
Overall, Djokovic leads the head to head 26-25, but Nadal won their most recent grand-slam meeting - the 2014 French Open final, in four sets. Isner is 8-3 against Anderson, and this will be his first career semifinal at a major.
Rafael Nadal has again showcased sympathy for his rivals by saying he "feels sorry" for Federer following his shock quarter-final exit at Wimbledon. "I've only lost one match", said Nadal.
"But also putting myself in these positions where hopefully I'm able to get another step forward and be playing on Sunday". After losing the second set, he turned into Vintage Djoker and won 12 of the next 16 games to return to the Wimbledon semis for the seventh time.
"I'm very, very happy to be in this position right now", said the ninth seed, who has never played on Centre Court at Wimbledon.
"I was very impressed that he could keep calm under all that pressure and push through".
Djokovic also added: 'I think it's good to have maybe shot clock for the warm-up, the walk into the court.