World number one Djokovic needs a Roland Garros title to become just the eighth man to capture a career Grand Slam.
Nadal, meanwhile, is just two matches away from becoming the first man in history to win the same major on eight occasions.
It's the match-up that most neutrals would have hoped to have graced Sunday's final, but Nadal's seven-month absence from the sport contributed to his number three seeding in Paris and hence a blockbuster semi-final collision beckons.
“I don’t give a damn who the favourite is,” Nadal told journalists at a press conference at Roland Garros.
“The winner will be the one who plays the best match.”
The 27-year-old Spaniard enjoys a 19-15 winning record over his Serb rival and, possibly crucially, a 12-3 edge on clay.
Furthermore, seven-time champion Nadal, who beat Djokovic in the final last year, defends a staggering record in Paris of 57 wins in 58 matches.
But Nadal is keen to play down the hype despite having arrived at the French Open with six titles from eight finals contested since his return to the tour in February.
He is also keenly aware that Djokovic, just one year his junior, relieved him of his Monte Carlo Masters title in April, a claycourt crown he had proudly worn for eight years.
"I didn't have ambition to win Roland Garros; I didn't have ambition to win Monte Carlo; I didn't have ambition to win Indian Wells," said Nadal.
"My only ambition is feel myself competitive another time, feel myself happy to play tennis another time, and try to play with no limitations. So that was my only ambition four months ago, three months ago.
"I am able to play with less pressure than before because I know I came from a very low situation, very low moments, so everything is positive for me."
Nadal has faced Djokovic more times than he has faced Roger Federer, whose disappointing quarter-final exit to Jo-Wilfried Tsonga only to served to fuel the speculation that the great Swiss is past his best.
But Nadal hinted that despite having faced Djokovic in five Grand Slam finals in under three years, his longer rivalry with Federer may have more prestige.
"The matches against Roger start to be classic ones because we always competed for important things, and that makes the matches interesting, emotional for us, for the crowd, and that makes the sport big," said the Spaniard.
Djokovic already has the Australian Open under his belt this year and, despite a brief lapse late in his straight-sets quarter-final win over Tommy Haas, there are not many cracks in his armour.
Haas, for example, won just one point off the Djokovic serve in the first set on Wednesday.
Djokovic believes his game, as well as that crucial psychological triumph in Monte Carlo, could be key on Friday.
"Everything has to work in harmony. Everything has to be synchronized and, you know, not many ups and downs throughout the match," said the top seed, who has lost all four times he has faced Nadal at Roland Garros.
"I played him in Monte Carlo, on clay. I played a fantastic match, and I know what it takes to win against him. That's what I'm going for. I'm going to win. That's the mindset."
The enormous expectation surrounding Nadal and Djokovic will be welcomed by Jo-Wilfried Tsonga who faces David Ferrer in the other semi-final as he continues his campaign to become France's first home champion since Yannick Noah in 1983.
Tsonga, who will be playing in his fifth Grand Slam semi-final, is looking to make his second final at a major following his runner-up finish to Djokovic in Australia in 2008.
"Everybody's expecting a lot from me since the beginning of this tournament — not only this tournament, but every day. So I'm used to it," said the 28-year-old sixth seed.
Ferrer, the fourth seed, made the semi-finals last year and has yet to make the breakthrough to a final and, at 31, the clock is ticking.
"I am really up for this meeting with Tsonga. It's my second semi-final at Roland Garros and it's a very important juncture of my career," said Ferrer, who has a 2-1 lead over Tsonga, including their only clash on clay in Rome in 2010.