Jose Mourinho's love affair with the Champions League has coincided with Real Madrid's demise in the competition but both will hope the chemistry is right this week as the Spanish club aim to end a last-16 jinx.
Nine-times European champions Real have not made it past the first knockout round since 2004 but after a 1-1 draw at Olympique Lyon in the first leg in France, coach Mourinho's side are well-placed to finish the job at the Bernabeu on Wednesday.
Holders Inter Milan, the club Mourinho steered to glory last season when they beat Bayern Munich in the final, are in grave danger of an early exit after the Bundesliga side won 1-0 in the San Siro in the first leg.
Should Bayern protect their advantage on Tuesday to gain revenge for their defeat in Madrid last May it would mean Italy are without a team in the Champions League or Europa League.
"We are still good enough to do a job in Munich and hold on to our crown," said Inter boss Leonardo, playing down the pressure.
"I don't believe we are carrying any particular burden for being champions. If anything it just makes us more motivated."
Also on Tuesday Manchester United host Olympique Marseille after a dour 0-0 draw in southern France left the tie delicately poised.
The week's other last-16 tie looks the most cut and dried with Chelsea having established a 2-0 lead against FC Copenhagen in the Danish capital two weeks ago.
When Mourinho won the Champions League for Porto against Monaco in 2004, fans of Real would have laughed off suggestions their club could spend the next six years as also-rans in the competition.
Last year's exit at the last-16 stage by Wednesday's opponents spelt doom for Manuel Pellegrini and paved the way for Mourinho to occupy arguably the hottest coaching seat in world soccer, tasked with plotting a route to a Wembley final in May.
With Barcelona seemingly unstoppable at the top of La Liga, all eyes will be on Real's Champions League progress under the Portuguese who once again demonstrated his knack for knockout glory last season when he outsmarted Barca in the semis.
Real have impressed in the tournament so far and warmed up with a 2-0 La Liga victory over Hercules on Saturday. They have won all 21 of their matches this season at the Bernabeu which Mourinho has turned into a fortress.
"The key for me will be playing with a 12th player," said the Portuguese, referring to the club's fans.
"It would be much easier. If the Bernabeu responds we will have won much in advance and we will also be stronger.
"Lyon are a very good team with experience and tradition in the Champions League. We will have to be in optimum form for the clash," added Mourinho whose striking options have been enhanced by the form of ex-Lyon striker Karim Benzema who scored twice against Hercules.
Frenchman Benzema said: "I want to score against Lyon. I feel much better than before. I am convinced we will defeat Lyon".
The omens do not look good for Inter who have failed to win their last four Champions League away games and conceded three goals in the last two -- against Tottenham Hotspur and Werder Bremen.
Inter have a major injury worry over former Bayern defender Lucio who was hurt in Friday's 1-1 draw with Brescia.
Bayern will be buoyant after a 6-0 hammering of Hamburg -- a win that moved them up to fourth in the Bundesliga.
Friday's draw for the quarter-finals will definitely include Barcelona, Tottenham, Schalke 04 and Shakhtar Donetsk after they completed aggregate victories last week.