One of the ties of the round sees Real Madrid travel to France to take on Paris Saint-Germain.
It again pits Cristiano Ronaldo against Zlatan Ibrahimovic and the Swede will be hoping for a different outcome to the one when the Portuguese tore Sweden apart in the World Cup play-off to reach Brazil in 2014.
This could well be the game in which the tables are turned.
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Bizarre as it seems with Real up at the top of La Liga, they've not played well. Indeed, they've huffed and puffed through games and at times looked quite sterile and ordinary.
That just won't do for Florentino Perez or Rafael Benitez.
Let's take a look at three things that could shape the outcome of this one...
Barcelona have enough problems with injuries, but Real's are something else.
Karim Benzema, James Rodriguez, Luka Modric, Sergio Ramos and Pepe are all either out of this match or face a race against time to be fit for it.
Real have remained unbeaten in La Liga and in Europe, but this game will be a real test for them.
It's highly likely that PSG will look to expose the defensive weaknesses that exist. How much longer can Keylor Navas get them out of jail?
Five times against Levante the keeper was required to stop a certain goal.
Even a draw would be an acceptable result given just how many first-teamers are in doubt on this occasion.
Like Real, PSG remain unbeaten this season.
Of the 12 games played in all competitions so far, ten have been won with two drawn.
At their Parc Des Princes home, the French champions have won five and drawn one, scoring 13 and conceding just three.
Perhaps more ominously for Real, they've kept a clean sheet in four of the six home games and scored at least twice in every one.
Benitez has been famed in the past for his defensive nous and it's fair to suggest that PSG won't have things all their own way in the attacking third. However, Zlatan will give Real's centre-backs the sternest test of their credentials so far.
How long they hold out for will author the final result of this game.
Ronaldo remains the highest scorer in the history of the competition.
With nemesis Lionel Messi sidelined for this and at least one more matchday, Ronaldo can surge even further ahead and cement his place in the Champions League record books.
It's clear how much being the best means to the player and you can be assured that he will be trying extra hard to add to his tally.
As central striker in the absence of Benzema, the likelihood of him being in the right place at the right time increases dramatically.
And it's unlikely that PSG will be able to keep him quiet for the full 90 minutes.
Who do you think will win this one and what will be the key difference? Give YOUR opinion in the comment box below!
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