Despite the frequency of these two European greats appearing in the later stages of the Champions League, tomorrow night will be only their ninth meeting.
The previous eight took place in the knockout stages of Europe's most prestigious competition and have produced two Manchester United wins, three Real Madrid victories and three draws.
Underneath the beauty and the brutality that have underlined this fixture spanning nearly 60 years, there have been 31 goals; however, only once did the English side progress.
Here are five of the most memorable meetings between the two teams.
April 24, 1968, Old Trafford. Manchester United 1-0 Real Madrid.
This was the third meeting between the two sides—the first in over 10 years and the semifinal of the European Cup.
Manchester United took the lead through George Best, the Irish forward turning home a cross from John Aston in the first half.
And as scoring went, that was that for the first leg.
Matt Busby's side held out for a narrow 1-0 win to take with them to Madrid, in what would prove a fascinating fixture the following month.
April 19, 2000, Old Trafford. Manchester United 2-3 Real Madrid (aggregate 2-3).
Manchester United would have been reasonably happy with a 0-0 draw in Spain on April 4, 2000, but Real Madrid's superb display in England sent the Red Devils crashing out of the Champions League.
United were unbeaten at home in 16 months, but an early Roy Keane own goal and two wonderful quick-fire second-half strikes from Raul Gonzalez left them with a mountain to climb.
David Beckham pulled one goal back, a brilliant individual effort, and Paul Scholes scored a late penalty, adding little other than a bit of credibility to the result.
Sir Alex Ferguson admitted (via BBC Sport), "The best team won on the night," as Los Blancos knocked out the holders en route to winning the competition.
April 24, 1957, Old Trafford. Manchester United 2-2 Real Madrid (aggregate 3-5).
The first meeting between the two teams was on April 11, 1957 in the semifinal of the second-ever European Cup.
At the Bernabeu, goals from Hector Rial, Alfredo di Stefano and Enrique Mateos would have had Madrid out of sight but for Tommy Taylor's strike for Manchester United.
With home advantage, a United side featuring Bobby Charlton and Duncan Edwards would have fancied their chances, but goals from Raymond Kopa and Rial soon had them 5-1 down on aggregate.
Taylor and Charlton leveled on the night, but Madrid advanced to the final, winning their second of five straight European Cups.
April 23, 2003, Old Trafford. Manchester United 4-3 Real Madrid (aggregate 5-6).
Following a 3-1 defeat at the Bernabeu, speculation about David Beckham's future and rumors of a boot to his face from Sir Alex Ferguson, this fixture was hotly anticipated.
It didn't disappoint.
Fans were treated to a match of seven goals, dazzling attacking football, a Beckham cameo from the bench and Ronaldo—the Brazilian one—in destructible form.
Guti opened up Man Utd's defense to set up Ronaldo for the opening goal, only for Ruud van Nistelrooy to scramble home an equalizer just before the break.
Ruthless Ronaldo soon put the game to bed, completing his hat-trick—his third a stunning drive past Fabian Barthez.
An Ivan Helguera own goal and a Beckham double—one a trademark free kick—salvaged little but pride for United, who won on the night but lost the tie.
May 15, 1968, Santiago Bernabeu. Real Madrid 3-3 Manchester United (aggregate 3-4).
Heading into the tie, the sides were separated by a solitary George Best strike at Old Trafford 21 days earlier.
Real Madrid raced out of the blocks, though, and Pirri, Francisco Gento and Amancio Amaro put them 3-0 up before an own goal just before halftime gave United a sniff.
"We're Manchester United, let's have a go at them," barked Matt Busby at the interval, and they certainly did.
George Best tried to add more, but it ended 3-3, and the Red Devils advanced to the final at Wembley, where they would eventually beat Benfica 4-1 after extra time.