It may not be El Clasico, and it's rarely been a classic in recent years, but the ramifications in the La Liga title race are no less important.
As the line-up in two of the last three Champions League finals, few fixtures hold more significance in world football than when the two sides of the Spanish capital collide.
This not just a derby though, but a clash of philosophies as Diego Simeone's relentlessly organised and ferocious counter-punching unit come up against Zinedine Zidane's collection of stars.
As the most recent Madrid representatives to win La Liga, Atletico no longer live in the shadows of their neighbours, commanding a dominant head-to-head recent domestic record.
Indeed, no side are more effective at nullifying Real Madrid's attacking threat, with Simeone's men mastering the art of neutralising Gareth Bale and Cristiano Ronaldo.
The stats make that clear. Ronaldo has failed to score in his last six Madrid derbies, while the only time Bale has found the net against Atletico was his extra-time winner in the 2014 Champions League final.
The two sides have met 11 times since that famous night of La Decima and Real have remarkably scored just seven times, recording their only triumphs in Europe, 1-0 on aggregate in the 2014/15 semi-finals and then on penalties last May.
However, Atletico haven't quite been their stringent selves of late, conceding in their last four games, while there's been a shift in how they approach home games since Kevin Gamiero arrived in the summer, with four or more goals scored in four of their seven matches at the Vicente Calderon.
Two loses from their last three in La Liga suggests that the transition has not necessarily been a smooth one and it will be interesting to see whether the French striker maintains his starting berth, having scored a modest five in 15 since arriving.
That's assuming his compatriot Antoine Griezmann is fit to feature after suffering a foot injury on international duty, but all indications suggest he will be ready for the game.
Perhaps the most important team news is, however, the one player who has troubled Atletico's defence more than most in recent years - Sergio Ramos.
The Spain captain has scored three times in the last 12 Madrid derbies, including the opener in last season's Champions League final.
He will also be a welcome return to Real's leaky backline, which recorded their first clean sheet in 11 games before the international break.
That defensive vulnerability has been countered by their ability to score two or more in all but two of their 17 games this season, propelling them to the top of La Liga and helping them maintain an unbeaten run in all competitions which currently sits at 28 games.
The question is whether Atletico will look to meet fire with fire or set up to spoil? Zidane will be hoping for an all-out gun fight, knowing that he has the superior weaponry.
Sky Bet: prediction: Real Madrid to win and both teams to score - 9/2