Real and Atletico are set to face each other in the final of the Champions League for the second time in three seasons this weekend in Milan.
In 2014, the encounter between the two sides ended in a 4-1 victory for the Los Blancos after Sergio Ramos' late equaliser forced extra-time, where Simeone's men were overwhelmed by a Real onslaught.
Since that night in Lisbon, a few things have changed for both sides which could provide a different sort of match-up this time around.
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Different manager at the Bernabeau
Real have seen a couple of managerial changes since the 2014 triumph.
Carlo Ancelotti was sacked at the end of the 2014/2015 season, being replaced by Rafael Benitez. After a disappointing campaign, the former Liverpool manager was let go and club legend Zinedine Zidane was appointed as permanent manager in January.
Atletico still have Diego Simeone at the helm and the Argentine does not look to be leaving the Vicente Calderon anytime soon.
In terms of managerial experience, Simeone has a head start over Zidane, having started his managerial career in 2006 with Argentine side Racing.
The former midfielder took charge of Atleti in 2011 and already has a La Liga title to his name with the Red and Whites.
Zidane, on the other hand, is relatively inexperienced as the gaffer but has had some experience as the assistant coach under Ancelotti and in charge of the club's reserve team, Real Madrid Castilla.
Despite Zidane's lack of experience as a manager, Real have improved considerably with the World Cup winner in charge, reaching the Champions League final and coming within an inch of winning the league title, which Barcelona eventually clinched after a tight three-way race.
Simeone is already touted as one of the best managers in the continent and has transformed this Atletico side into a formidable force in Europe.
It'll be interesting to see which of these two young managers can win the tactical battle in Milan.
Changes at the Bernabeau
To the surprise of many, Angel di Maria, who was one of Real's biggest threats during his time at the club was sold after the final in 2014, a game which Di Maria produced a stunning performance - bagging the man-of-the-match award in the process.
Another top player who the club parted ways with in the last two years was Xabi Alonso - another instrumental figure in winning the Champions League two years ago.
World Cup winner Sami Khedira also departed for Juventus in 2015 in search for more first team action.
Club captain and icon Iker Casilas was unceremoniously released from the club and sold to Porto, after losing his place in the first team.
Despite the loss of the above key players, Real brought in big names such as Toni Kroos, Keylor Navas and James Rodriguez after their outstanding performances in the 2014 World Cup in Brazil.
However, Real's biggest assets remain the front three who have scored 99 goals between them this season. Cristiano Ronaldo, Karim Benzema and Gareth Bale have lifted the club during the second half of the season and could cause Atletico some trouble if in sync during the final.
Atletico have maintained high standard despite departures
It is astonishing how Atletico have managed to maintain the same level of performance considering the departure of several key players to other clubs over the last two years.
After their Champions League final showing, a season in which they also won the La Liga, Diego Costa, Thibaut Courtois and Felipe Luis were all snapped up by Chelsea, although the latter is now back at the Calderon.
Toby Alderweireld, Miranda, David Villa and Arda Turan have all departed which had led many fans to fear the club would potentially crumble.
Nevertheless, Atletico have gone from strength to strength and are arguably in an even better position to beat Real than two years ago.
Fernando Torres is back at the club and the former Liverpool and Chelsea man has re-invented himself at his breakthrough club, reaching 100 goals for the side in the process.
Goalkeeper Jan Oblak has been a revelation and the 23-year-old looks set to become one of the best keepers in Europe after a promising season.
The signing of Yannick Carrasco and the emergence of 19-year-old Spanish sensation Saul Niguez has also helped them march through to the European final.
However, the biggest change since the final in Lisbon and something that could even be the deciding factor in the upcoming final is the presence of Antoine Griezmann.
The French forward has been exceptional for Simeone's side since signing in 2014 and has registered 57 goals for the club in all competitions. If Real can keep him quiet, it will go a long way to nullifying Atletico's most potent threat.
Another key difference between this final and the last is that both Costa and Turan, two of Atletico's best players during 2013/2014, were injury doubts before the game and not fully fit.
Costa was forced to limp off in the first half of the final itself, greatly subduing their attacking prowess.
This time around, Atletico are expected to be at full strength and on their day, Simeone's side are one of the toughest teams to break down.
Oblak and his loyal defence kept 24 clean sheets from their 38 league games this season and also shut-out free-scoring Barcelona and Bayern in the home legs of their Champions League clashes.
Despite Atletico's strength, Real are always favourites to win the Champions League due to their rich history in the competition, and will enter the finals expected to win.
Will Simeone's men be able to upset the odds this time around? We will find out in a few days time.