It is almost a pity that two of the biggest, best-supported football clubs are destined to meet so early in Champions League competition—the fixture could just as easily have been a semi or even a final.
The first match of the two-leg tie takes place in Madrid at the Bernabeu in front of a crowd that is sure to provide a raucous atmosphere for the clash.
The coaching duel between Jose Mourinho and Sir Alex Ferguson will attract plenty of attention, and the tactics they deploy.
This article will seek to predict the two managers' starting lineups for their respective sides.
With four days rest to the Red Devils' three, Mourinho's side should be the more refreshed. But these are superior athletes we're talking about—an extra 24 hours to recuperate shouldn't be a significant factor.
There can be no doubt that Real's strongest XI according to the Portuguese coach will be named.
New signing Diego Lopez will start in goal, while the back four virtually picks itself.
Fabio Coentrao and Alvaro Arbeloa will start at full-back, with Sergio Ramos between them. The only tough decision will be whether or not to stick with prodigious, young centre back Raphael Varane or to play the controversial Pepe.
For my money, Mourinho may go against popular opinion and start Pepe—the more experienced of the two and a favourite of the boss.
Supreme holding midfielder Xabi Alonso will play alongside German Sami Khedira to form the spine of the team, with Mesut Ozil ahead of them in the central playmaker role.
Angel Di Maria will spend most of his evening marauding down the right flank, but Cristiano Ronaldo will look for every opportunity to drift inside from the left and threaten from a more central position.
This will see Karim Benzema often drift out to the left, but the French striker has been a terrific creative threat at time this season there, and should not be overlooked by United's Rafael.
In terms of formation, Real should on paper setup in a 4-2-3-1, but naturally things will become more flexible as the game wears on.
Sir Alex will have given himself a welcome selection headache for the game following the terrific performance of Phil Jones against Everton at the weekend.
The young Englishman man-marked the Blues' danger man Marouane Fellaini out of the 2-0 win, and could very well be asked to fulfil the same task against Ronaldo.
Both he and Jonny Evans picked up minor knocks in that game, but should be fighting fit by Wednesday.
Nemanja Vidic, Rafael and Patrice Evra are all in excellent form, and are no-brainers to start at the Bernabeu.
If Jones does play in midfield, the formation could resemble a 4-1-4-1, or with Rooney pushing into attacking midfield, a more traditional 4-2-3-1.
Michael Carrick will certainly play in holding midfield—he has come on in form quite magnificently since the new year.
With Ashley Young yet to return from injury, and Nani still too inconsistent to be relied upon, Shinji Kagawa could be included in the team, playing on the left side of the pitch in a role he has occupied several times for the Japan national team.
Antonio Valencia is likely to play on the right flank, with goal scoring extraordinaire Robin van Persie as the lone striker.
The likes of Tom Cleverley, Anderson and Javier Hernandez may earn a surprise nod, but it's difficult to see any of them, especially the latter two, starting the game anywhere else but sat firmly on the bench.
So there you have my predictions for who will take the field this week. Feel free to leave your own predictions in the comment box.
Picking a winner would probably prove a more difficult task at this point.