World number one Nadal, the 2008 and 2010 champion at the All England Club, trails Djokovic, the 2011, 2014 and 2015 winner, 26-25 in a rivalry which began at Roland Garros 12 years ago.
Along the way, they have fought out a series of classic and epic battles including Djokovic's 5-7, 6-4, 6-2, 6-7 (5/7), 7-5 Australian Open final victory in 2012.
At five hours and 53 minutes, it was the longest final ever at a Slam. The following year, Nadal downed the Serb, who was world number one at the time, 6-4, 3-6, 6-1, 6-7, 9-7 in the semi-finals in Paris, this time in four hours and 37 minutes.
"It's always a big challenge to face Novak," said 32-year-old Nadal who is back in the semi-finals at Wimbledon for the first time since 2011 when he finished runner-up to Djokovic.
"He is one of the more complex players that I ever saw in our sport. You know that you can't win against him if you don't play very well."
Nadal is chasing an 18th Grand Slam title which would put him just two behind Roger Federer who was sensationally knocked out in the quarter-finals by Kevin Anderson.
For his part, Djokovic is eyeing a 13th major after making the semi-finals of a Slam for the first time since finishing runner-up at the 2016 US Open. This time last year, few would have expected to see either man back in the last-four at the All England Club.
Nadal was knocked out in the fourth round, losing 13-11 in the final set to Luxembourg journeyman Gilles Muller.
On four of his previous five visits to south-west London, he had been defeated by players outside the top 100.
When he lost in the French Open quarter-finals to world number 72 Marco Cecchinato last month, he even suggested he was ready to skip Wimbledon this year as his ranking slipped to 22, his lowest since August 2006.
But the 31-year-old has been rejuvenated at Wimbledon, sweeping into the semi-finals for the eighth time.
- 'Not up to standard' -
"My results were not up to the standard that I had before," said Djokovic after beating Kei Nishikori in the quarter-finals.
"At the same time, I'm trying to use the experience and memories that I have of being in the final stages of Grand Slams, just take things very simple, day by day."
Nadal had not dropped a set at the tournament until the quarter-finals where he fought back to defeat Juan Martin del Potro 7-5, 6-7 (7/9), 4-6, 6-4, 6-4 on Wednesday.
That four-hour and 48-minute epic put him into his sixth Wimbledon semi-final and 28th at the majors.
Friday's other semi-final pitches Anderson, the eighth seed who lost to Nadal in last year's US Open final, against ninth-seeded American John Isner. Both men are in the semi-finals at Wimbledon for the first time.
Anderson is the first South African to make the last-four since Kevin Curren in 1983.
The surprise presence of Anderson and Isner means this year's Wimbledon semi-finals will feature players all over the age of 30 for the first time in the Open era.
Their clash, however, may not be easy on the eye.
Isner hasn't been broken in 95 service games and has fired 161 aces,fuelled by a sweet tooth.
"I think after each win throughout these 10 days, I've had a Kit Kat. I'm not going to change that now," said the American.
Anderson has 123 aces to his name.
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