A victory for the Bernabeu showmen on Sunday at the Vicente Calderon, coming under three weeks after Real knocked holders Atletico out of the Copa del Rey there, might provide just cause for Diego Simeone's club to request an ASBO.
The big Madrid derby may not be a title decider, but it could knock Atletico almost out of the running and leave Real in a shoot-out with Barcelona, yet again, for the all-important silverware. Real start the weekend with a three-point cushion over both Barcelona and Atletico.
Cristiano Ronaldo's three-match Primera Division suspension has reached a timely end in time for the occasion, and Real warmed up with a 6-1 victory at Schalke in the Champions League on Wednesday to serve notice of their threat.
Not that Atletico would not have been prepared in any event, but they know the side that will make the short hop southwards through the city are coming with the intention and wherewithal to inflict more damage.
Koke, who together with Atletico team-mates Diego Costa and Juanfran received a Spain call-up on Friday, ahead of next Wednesday's friendly against Italy, insists Atletico are determined not to play the role of the poor relations this weekend.
"I always enjoy playing against Madrid, especially if you can beat them," said Koke. "We will go to the match facing it as we do with all our games, as if it were a final.
"No one is invincible in this world. They are very good at defending and in attack they also have many important players. We will face a great team but we will try to do our best. It will be a great match to watch."
Ronaldo, Karim Benzema and Gareth Bale all scored twice against Schalke, and their vaunted B-B-C - Bale-Benzema-Cristiano - forward line could again be deployed on Sunday.
Ronaldo's suspension stemmed from his red card at Athletic Bilbao, and he remains irked to have been kept off the pitch for recent league commitments, even though Madrid have coped admirably in his absence, winning all three games without the Portuguese forward.
"What happened has happened. I am frustrated by it, because what I did didn't deserve a three-game ban, but I am very happy to return and score twice (against Schalke)," Ronaldo told his club's official website.
"We are up for the derby, we are Real Madrid and we will give our best and try to win."
Barcelona will have two hours to digest the result from Madrid before they tackle Almeria on Sunday evening.
Gerardo Martino's team have taken time to reflect on their painful 3-1 defeat at Real Sociedad last weekend, and anything less than three points from their Nou Camp tussle with a team lying just outside the relegation zone would be an equally jolting setback.
"We've had a week to rest," said midfielder Cesc Fabregas, "And that's vital to recover good vibes and the top spot of the table, where we want to be. On Sunday there can be no excuses."
Real Betis need to transpose their Europa League form into Sunday's Primera Division lunchtime game at Villarreal, as they look to find the winning run that could offer them a glimmer of hope at the foot of the table.
The Seville club eased through to the Europa League last 16 by beating Rubin Kazan on Thursday, but in the domestic league they have won just three times this season, and their situation is becoming increasingly hopeless.
Betis too have neighbours to be envious of, with Sevilla standing seventh ahead of a home clash on Sunday with Sociedad.
In-form Valencia, who are undefeated in eight games and climbing the table gradually, will hope to nudge above Sevilla with a win at Rayo Vallecano, also on Sunday, while Saturday's fixtures see Elche play Celta Vigo, Espanyol travel to Getafe, Osasuna go to Levante, and Malaga have home advantage against Real Valladolid.