In what could be one of the greatest upsets of the season or yet another Champions League meltdown for Milan, Barcelona need to overcome a 2-0 aggregate deficit against the Rossoneri at their vaunted Camp Nou stadium.
Here are eight predictions before this epic Champions League clash, which will draw a worldwide audience.
A jittery Milan side can expect a Barcelona blitzkrieg right out of the gates.
The Catalans will fire on all cylinders, hoping to get an early score to really shake the confidence of the Rossoneri.
With Giampaolo Pazzini out, Milan's whole tactical approach changes drastically, as they'll play with no reference point up front, hoping to test Barcelona's defense with a lightning-fast counter attack.
Massimiliano Allegri took notes out of the defensive playbook of Jose Mourinho when his Inter side managed to beat Barcelona a few years ago in the Champions League.
Holding onto a 2-0 aggregate lead, Milan will need another admirable defensive effort if they are to go on to the next round.
The word is out: Lionel Messi doesn't do well against Italian teams.
Having scored only three penalty kicks in 10 matches against them, Serie A sides have built a reputation of having the perfect recipe to stop the four-time Ballon d'Or winner.
In the first leg, he wasn't allowed to get the ball near the area and found himself isolated far on the wingin places where he couldn't cut to his favorite left foot and put Christian Abbiati in danger.
When packed to the brim, the Camp Nou is one of the most formidable stadiums in the world.
Holding nearly 100,000 frenzied Blaugrana spectators, a rather inexperienced Milan side will be trembling during the introductory Champions League anthem.
Stephan El Shaarawy is one of the reasons Milan has had a near-historic turnaround in Serie A.
As their leading goalscorer, the 20-year-old prodigy most affectionately known as "Il Faraone" will have to carry the Rossoneri on his back. He was the catalyst behind Milan's second goal, when he found the treaking Sulley Muntari to put Milan up 2-0 against Barcelona in the first leg.
Milan's coach, Massimiliano Allegri, was viewed as the scapegoat in the beginning of the season when his team was near the relegation zone in Serie A.
Many fans called for his head and demanded change, but the club's president, Silvio Berlusconi, and CEO, Adriano Galliani, are not ones to sack coaches—the last midseason firing took place more than a decade ago when Fatih Terim was sent packing.
Giampaolo Pazzini will not be with the team after not being able to fight off Friday's injury.
He played a very underrated part in their first leg against Barcelona, taking a beating up front but holding up play well and giving Milan a point of reference.
Unfortunately, last Friday he succumbed to a bad knock against Genoa, resulting in a deep bone bruise. In his place, expect to either see M'Baye Niang (who will play on the right wing, forcing Kevin-Prince Boateng to the middle) or a complete formation change by Allegri.
No matter how the second-leg affair between Barcelona and Milan finishes, it surely won't be short of emotions, and it will be enthralling for neutrals.
This match is riddled with interesting subplots. Here's one last point to chew on—Milan got off to their worst ever start in team history this season, while Barcelona have been a complete antonym, as they had their best ever start.