Sir Alex Ferguson takes his Manchester United side to the Santiago Bernabeu knowing a positive result will put them in the driving seat to progress to the quarter-finals of the Champions League.
Spanish international David De Gea has proved himself to be the number one for the Red Devils this season, and will get the nod between the sticks for the first leg of the last 16 tie.
Rio Ferdinand was rested for the weekend win over Everton and will return to the heart of the defence alongside Nemanja Vidic, with Rafael and Patrice Evra certain starters at full-back.
In midfield, Ferguson has plenty of options, with Michael Carrick, Tom Cleverley and Phil Jones the probable midfield three. The later will be asked to keep close quarters with Cristiano Ronaldo throughout proceedings.
That leaves Robin Van Persie to lead the line through the middle for Manchester United, with Wayne Rooney and the industrious Shinji Kagawa expected to do their work from the wide areas.
A 4-3-3/4-5-1 formation that could easily switch to 4-4-2, the pressure will be on Madrid to make the running as the home side.
Manchester United predicted line-up v Real Madrid:
David De Gea; Rafael, Rio Ferdinand, Nemanja Vidic, Patrice Evra; Michael Carrick, Phil Jones, Tom Cleverley; Wayne Rooney, Shinji Kagawa, Robin Van Persie.