A time when its two best teams collide, and when planet football stops whatever it's doing and sits down to enjoy the spectacle.
This particular edition will be no different given what is ultimately riding on the outcome.
If Zinedine Zidane's side lose the match and subsequently fall 13 points behind their archrivals, can the Frenchman have a realistic claim on the top job after the end of this season?
Equally, should Barca rescind their record-breaking unbeaten record that stands at 39 games, could the jolt to their season be confidence-sapping enough to see a late-season blip?
However things pan out overall, the make up of the 90 minutes will be authored by mini tussles all over the pitch.
And none will be more important than that between the feistiest of pairings. Luis Suarez and Pepe continue to walk a disciplinary tightrope but are still the highest quality exponents in their respective roles.
The Portuguese has worked hard to keep Raphael Varane out of the side, and perhaps it's the extra edge that he brings—not to everyone's taste, mind—which has curried favour with Zidane.
Los Blancos certainly need a fighter or two in their ranks at this juncture. Players that are a little more physical and let the opposition "know who's boss."
Pepe has his detractors, but that conveniently glosses over the excellent defensive job he does for Real Madrid alongside Sergio Ramos.
Marcelo will be particularly in his debt given the excellent covering work he does for the team in that area of the pitch.
On this occasion, Pepe will be pushed to his physical and mental limits, and the latter is where he might fall short.
Suarez, himself no stranger to controversy, is hoping to fire Barca to a second successive league title and grab himself the Pichichi Trophy in the process. And he will take any given opportunity to get one over the defender.
Just one or two words to get under the skin of a notoriously short-fused player should be enough to place the advantage even more in favour of the hosts.
If Ramos hasn't recovered from the injury sustained while on international duty, then Varane will have to partner Pepe—a pairing that has been shown to be reasonably competent in the past, but nothing special.
Once Barca smell blood—and they will—Real are likely to be on the rack for long periods of the game, and there's no one better qualified than Suarez to pick up on any scraps.
In the form of his life, the striker won't give Real's back four a moment's piece. Any mistimed tackle will be met with an early card—thus rendering the recipient moribund in his duties for the rest of the game.
Suarez's ability to go either way when in possession of the ball, or when fed to him, is what should see him bypass a static Pepe with ease. The defender will look to show him inside, where Real can double up on the Uruguayan, but he's a little bit cuter than that.
Suarez's strength remains one of his biggest assets, and so backing in and climbing all over anyone in white shirt, but particularly Pepe, will be a prerequisite. His presence centrally can also curtail the Portuguese's forays into Barca territory.
Seventeen goals in his last 15 games as well as eight assists and three man-of-the-match awards, per WhoScored.com, evidence a centre-forward at the peak of his powers.
Stop him, and Pepe potentially stops a rout.