Let's be honest right from the get-go -- Milan aren't favored in this tie, and Atletico Madrid are doing a hell of a lot better than The Rossoneri when it comes to their respective leagues.
Atletico are tied for first with Spanish giants Barcelona and Real Madrid in La Liga, and Diego Simeone's men are exceeding expectations to say the least.
Simeone also played a chunk of his career over at Inter, so there's no love lost here.
It must be noted that the Madrid side have not yet lost in the tournament, and have only lost twice in La Liga -- sharing the same amount of losses with their Madrid rivals and Barca.
Here are five things to be wary of ahead of Wednesday's clash:
The Shaky Backline: The thing is we have no clue which players are getting the start on Wednesday when it comes to our defense.
For what it's worth, Adil Rami has experience playing in Spain, so it's safe to say he should be a starter.
We hope Mattia De Sciglio gets the start, and something tells us that if Cristian Zapata is fit, he should be chosen ahead of Philippe Mexes in the center (hence his Villareal days). Ignazio Abate should also be given the chance to shine, too, but there's no guarantee he'll start.
The rest is up in the air.
Diego Costa: The main reason why Atletico is surging right now is largely due to the dynamic striking abilities of Diego Costa.
Call him Spanish; call him Brazilian...it really doesn't matter.
The dude has 21 goals in 24 games, and he is becoming one of the best strikers in the world at the tender age of 25. A big move for him seems evident in the next couple of years, however he's Milan's problem on Wednesday.
Obviously Milan needs to watch him like a hawk, however they also can't pay too much attention to him, either. There are other weapons on the squad, as we touch base with them below.
Costa has started three games in the tournament, and has bagged four goals with one assist. His goal mount is the second highest in La Liga, right behind Cristiano Ronaldo.
Diego Ribas: The other Diego, known solely as Diego, is no stranger to il Diavolo.
The last time Milan had a season as poor as this one was the 2007-2008 campaign, which resulted in the Rossoneri playing in the UEFA Cup. They were matched up against Werder Bremen in the round of 32.
The first leg was touted to be a mismatch, with beloved striker Filippo Inzaghi finding the net in the 36th minute of the first leg.
At the 84th minute, Diego slotted home the ball behind Dida to cancel out Milan's away goal.
All hell broke loose in the second tie, as Claudio Pizarro netted two away goals in a 2-2 tie, with Werder Bremen advancing in the tournament (and to the final) by knocking out Milan early.
Diego went on a slump years later, but he's reborn on loan at Atletico. If history tells us anything, it's that psychological impact is also a factor in these big games.
Koke: It wasn't long ago that Milan was flirting with the idea of Koke joining the squad in the January Transfer window (amongst interest from Manchester United and Liverpool, as well).
The young Spanish midfielder has played 23 games for his club this season, scoring four goals and has nine assists to his credit.
He has the ability to bring the ball up with speed, and somehow makes his way up the field as the only man left ahead of the keeper.
He's deadly when he's on, and a player of his caliber can be a nightmare for Milan if the midfield fails to neutralize him before he gets to the defenders.
Eagerness To Attack: With Kesuke Honda ineligible to play for Milan in the tournament, that leaves us with Mario Balotelli at the forefront, surrounded by Kaka, Giampaolo Pazzini and Adel Taarabt (Robinho is out) -- depending on who coach Clarence Seedorf sees fit to start.
Seedorf praised Milan over the weekend for their narrow win over Bologna, and insists on an attack-minded team moving forward.
That's exactly what they need to do against the Spanish hopefuls.
The team just can't be afraid of Atletico's attack, and they need to get in their faces right from the start.
If Atletico scores first and gets that crucial away goal, it's bad news.
Milan was able to survive a group stage with Barcelona in the pack just a few months ago. Spanish opposition has never been an easy task for Milan, yet results have become unpredictable over the years in games against Spanish clubs.
That right there can be seen as a positive for the struggling Milan side.