Jose Mourinho of Madrid will face his former rival, Alex Ferguson of Manchester United.
The fixture for many is biggest and thus means one of the top favourites will be exiting the competition earlier than expected.
United were untouchable leaders in the group phase while stuttering Madrid finished second behind German Champions, Dortmund, in their own group.
With the La Liga title now out of the reach of Madrid, nine times European Champions, it is expected that Champions League will be their key target.
Meanwhile the other English team still in the race, Arsenal, have also been handed tough opponents as they are billed to face last year’s runners-up, Bayern Munich, for a place in the quarter-finals of the competition.
While in other fixtures, Efe Ambrose’s Celtic will face Italian champions Juventus, who helped knock holders Chelsea out of the competition at the group stage.
Elsewhere in the draw, a mouthwatering fixture is on the card as two European heavyweights, AC Milan and Barcelona, go head-to-head for the right to reach the quarter-finals.
The other duels see Malaga facing Porto and Shakhtar Donetsk going up against Borussia Dortmund.
The two remaining matches see Galatasaray facing Schalke which has a Nigerian, Chinedu ogbuke, in their books; while Paris St Germain have been drawn against Spanish side, Valencia.