The La Liga champions will play the first leg at their home ground, the Bernabeu Stadium, and in all likelihood, should come away with some sort of advantage from it.
However, Sir Alex Ferguson-coached teams are always tough to break down, and this year's squad has been one of his greatest ever, with new boy Robin van Persie the perfect complement and addition to Wayne Rooney in the club's attack.
They will definitely fancy their chances against the third-placed Real Madrid here given their inconsistencies throughout the year, and will be looking to try and gain some sort of advantage that they can take back to Old Trafford for the return leg next week.
Here's the biggest keys for Los Blancos to ensure that doesn't happen, and that they walk away from the Bernabeu Stadium with a win under their belt.
Perhaps the biggest need for Real Madrid throughout the first leg of this Champions League tie is not to allow the United attack to truly ever get off the ground.
So often this year the Red Devils have netted in the opening 15 minutes of play (12 goals in 26 Premier League matches and then 12 in the next 15 minutes also), and it's therefore little wonder that they find themselves streaking ahead on top of the table.
If Real Madrid can force Van Persie into isolation at the top of the attack, expect to see the Spanish side run out winners in the end of this one. Cutting off the supply to the clinical Dutchman will be the most pressing need for Madrid's defense and if they can do that, they'll go a long way to coming out with a victory in this one.
Utilize their speed in attack
Rafael Da Silva most likely will get some defensive help against Cristiano Ronaldo for the majority of the match, be that from someone like Michael Carrick or Phil Jones in defensive midfield or from the right centre-back, whoever that might be.
Whatever the case, that coverage should give Madrid a nice one-on-one on the other side of the field against Patrice Evra, who was shown to be a little exposed in coverage a couple of weeks back when trying to shut down Aaron Lennon of Tottenham Hotspur.
In that game, United had shifted much of their defense to the left in order to control Gareth Bale, yet they often left Evra exposed in single coverage as a result without the help in behind. Lennon was able to use his swift dribbling ability to blow past Evra a couple of times and cause real havoc for United's defense at the back because of it.
Angel Di Maria has a real chance here to become somewhat of a difference-maker for Madrid as a result here, especially if he can get in behind Evra once more. Look for Madrid to try and use their speed out on the right in particular to challenge United's defense here, as well as through their superstar, Ronaldo, on the left.
Force Wayne Rooney back into midfield
As Everton can attest to following their 2-0 loss in the English Premier League last weekend, Wayne Rooney is at his best when he's given the ball just ahead of the midfield line, but far enough down the pitch that he is separate from the attack.
That gives the England international time to run at the defense and choose his options—either out wide to the wingers, keep it himself or look ahead to Van Persie—and it makes it an absolute nightmare for defenses to try and cover.
Forcing him just that little bit further back down the field into more of a central midfielder role then will be key for Real Madrid, for it will allow the likes of Sami Khedira and Xabi Alonso to pick up Rooney in their defensive midfielder roles, rather than waiting for him to arrive to the defensive line.
With United most likely to utilize Tom Cleverley somewhere in central midfield, forcing Rooney back into a similar role will likely clutter the middle of the park for Madrid and allow their defensive line to sit a little higher than usual. That, in turn, will help cut off some of the supply and space for Van Persie at the top of the attack, as mentioned before.
If they can stop Rooney and block his space with either Madrid defenders or United teammates even, the Spanish giants will go a long way to eliminating the effectiveness of the Red Devils' attack and winning this match as a result of it.
Who do you think will win—Real Madrid or Manchester United?
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