Only Don Budge, in 1938, and Rod Laver in 1962 and again in 1969, have achieved the feat of holding the Australian Open, French Open, Wimbledon and US Open trophies at the same time.
Now world number one Djokovic is just seven matches away from joining that exclusive club.
There's only one problem and it comes in the shape of Nadal, who will become the only man to win seven French Open titles if he triumphs again on Roland Garros' famed red brick courts.
"This is a unique opportunity that very few tennis players have in their lives. I'm aware of that, but I accept it as a challenge," said Djokovic, ahead of the tournament which starts on Sunday.
"It makes me even more motivated. It makes me feel good about it, rather than feeling pressured and worried if something bad is going to happen."
Since Laver's 1969 achievement, only Pete Sampras, Roger Federer and Nadal have had opportunities to complete a non-calendar year Grand Slam.
Sampras lost to Jim Courier in the quarter-finals at Roland Garros in 1994; Federer lost to Nadal in the final at the 2006 and 2007 French Open while Nadal lost to David Ferrer in the quarter-finals at the 2011 Australian Open.
Djokovic defeated Nadal in the finals of Wimbledon, the US Open and this year's epic Australian Open to arrive at his date with destiny.
Until the start of the claycourt season, he had also beaten Nadal in a total of seven successive finals.
But world number two Nadal has since defeated the Serb on clay in the finals in Monte Carlo and Rome.
Roland Garros remains the only major where Djokovic has yet to make the final.
Three times the 25-year-old has been a semi-finalist, losing to Nadal in 2007 and 2008 before seeing a remarkable 43-match winning run ended by Federer at the last-four stage in 2011.
Ten-time a Grand Slam title winner, Nadal, 25, has a remarkable CV at the French Open -- six trophies in 2005, 2006, 2007, 2008, 2010 and 2011 -- and a match record of 45-1.
His only blip, a 2009 fourth round loss to Robin Soderling, came at a time when he was plagued by the acute knee problems which have often threatened to overwhelm him.
This season, Nadal has, once again, been surpreme on clay and arrives in Paris boasting a 16-1 record on the surface.
But the Spaniard is keen to play down talk of a seventh French Open.
"I have much more than I ever dreamed," said Nadal."I am coming here every year with the motivation to play well. But I am not going to be more motivated because I have six and I can win seven.
"The motivation always is the same -- sometimes you lose; sometimes you win. That's sport and that's the game."
Despite his 31st birthday fast approaching, and with the last of his 16 Grand Slam titles won at the 2010 Australian Open, there is little indication of Federer losing his powers.
The Swiss world number three was the man to benefit when Nadal slumped to his stunning 2009 loss in Paris, taking his first and only French Open title.
This will be his 14th French Open appearance. After making his debut in 1999, it took until 2006 for him to reach his first final -- the first of three successive title match defeats to Nadal.
After ending Djokovic's winning run in the semi-finals last year, he fell to a fourth final loss to his great Spanish rival.
The Swiss took the Madrid blue-clay court title -- one of four trophies this year -- and cruised through the Rome Masters until he ran into Djokovic in the semi-finals.
And Federer believes Djokovic will be thwarted in his attempt to make history.
"Rafa is the favourite for me," said Federer. "He's playing for his seventh title, so no discussion. We're crazy to even talk about this. Some people might say he's not the favourite, but to me he's the favourite."
World number four Andy Murray heads into the French Open, where he lost to Nadal in last year's semi-final, with question marks over his fitness after he revealed that he has been carrying a back injury since December.
His claycourt season has reflected his physical frailities -- quarter-final exits in Monte Carlo and Barcelona followed by a third round loss in Rome.
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