It has become the biggest derby in the Champions League. Seven times they have clashed in Europe and each occasion has been agonising for the underdogs.
This contest has always been decided by the tightest of margins, even the 2014 final which finished 4-1 to Madrid but which Atletico were winning until the third minute of added time.
Extra-time was the killer then, and Atletico were also cruelly denied in last season’s final when Juanfran’s kick hit the post in the shoot out, Antoine Griezmann having already struck the bar with a penalty start of the second- half.
So near but so far has always been the story for Atletico, right from the start, when they recorded their one victory. Nowadays that 1-0 scoreline, after a 2-1 defeat in the first leg at the Bernabeu, would have sent them through to the final on away goals.
Back in 1959 there was no such rule, nor was there extra-time, and Real Madrid won the replay.
Tonight’s match could provide the underdogs with the platform for some long-awaited revenge. Real Madrid start, yet again, as favourites. They have more potential match-winners, and better options on the bench.
Yet they are vulnerable at the back and would almost certainly not be playing this semi-final but for the aberrations of the referee, Victor Kassai, in their match against Bayern Munich.
Which brings us straight to one of tonight’s big questions: will Casemiro keep his head?
Against Bayern he was extraordinarily fortunate to avoid a second yellow card, and he was also lucky to avoid a double yellow against Barcelona in their epic league match nine days ago.
The Brazilian is a key man for his team, but he has now collected 13 bookings two seasons running. The season before that, when he was on loan at Porto, it was 15.
Somehow Casemiro has avoided being sent off since he arrived in Europe four years ago, but he has been walking a tightrope recently. Atletico are bound to target him.
Diego Simeone had a chequered past as a player himself, and also knows all about getting opponents into trouble. Martin Atkinson, tonight’s referee, will need his wits about him.
Real Madrid’s fragile defence will also be tested by Griezmann and Kevin Gameiro. They concede goals almost every time they play – 67 in 53 matches, which is 28 more than Atletico.
Without Pepe, Zinedine has to choose who will partner Sergio Ramos at centre back – Nacho or Raphael Varane. Varane is the safer option, but the manager has a doubt about his state of mind.
“He had a very long and complicated injury,” said Zidane. “From time to time he hurts something and I do not know if it is mental or something else.”
Keylor Navas in goal may also be a concern. He was brilliant against Barcelona, although he still let in three, but he does not provide quite the sense of security to his back line that Jan Oblak does for Atletico. Navas this season has conceded twice as many goals as Oblak.
So the champions are vulnerable, but that’s partly because their full-backs play a crucial role in their attack. Danny Carvajal and Marcelo have set up 21 goals between them and Marcelo has been in rampaging form recently.
That is a worry for Atletico because their defensive options are limited on the right, with two players sidelined and the Croatian Sime Vrsaljko possibly out injured.
Real Madrid’s strength in the air also gives them an edge. They have scored 38 times from headed goals this season. Casemiro and Varane are both a threat at set pieces, as is Cristiano Ronaldo, who scored three times in last November’s derby.
But the man who haunts Atletico is still Ramos, their nemesis in 2014 and again last season, when he became the first defender to score in two Champions League finals. His leadership could once again prove to be the difference between the two sides.