Bayer Leverkusen will be out for revenge after the Spanish side knocked them out of the competition two years ago. Following an undefeated run in the group stage they may be in luck.
European football has been a welcome respite from the inconsistent, chaotic world of the Bundesliga for Bayer Leverkusen fans this season.
Roger Schmidt's (pictured above) side currently sit eighth in the German top flight with four wins and four defeats in their last 10 games, yet their Champions League form has looked far more impressive: with an undefeated run over the entire stretch of their campaign thus far.
With somewhat unexpected wins over Tottenham Hotspur and Monaco and four draws from the remaining games the German side finished second in Group E behind Monaco. And after showing an uncharacteristically pragmatic approach to the competition and an appetite for upsetting the odds, there is plenty to suggest they're up for a fight.
"Why not win against them?" said Leverkusen goalkeeper Bernd Leno. "If we show our Champions League face, then everything is possible.
"You can see the team really wants it. We are fighting, we are fighting for each other and that was not necessarily the case a couple of weeks ago."
Yet on Tuesday night the German side comes up against what will undoubtedly be their toughest opponents yet in Atletico Madrid. The 2014 finalists topped their own group with just one defeat and five wins in six matches, finishing above Bundesliga champions Bayern Munich.
Indeed Leverkusen fans will need no reminder of what the Spanish side are capable of as both sides met at this exact stage two years ago, with Atletico going through on penalties after each claimed a 1-0 in front of their own fans.
"Atletico has strengthened further since our duel two years ago," lamented senior striker Stefan Kiessling, referring to the club's signings of continental stars such as Jackson Martinez, Nico Gaitan and Kevin Gameiro in the past two seasons.
Yet Schmidt will be able to call upon stars of his own. Karim Bellarabi's goal in Friday's 3-1 win over Augsburg complimented the two assists he claimed the week before, as starts to rediscover his form after recently returning from a long-term injury, while young stars Julian Brandt, Benjamin Henrichs and Kai Harvetz have repeatedly excelled.
Leverkusen will be without Jonathan Tah and Lars Bender through injury, but can rely upon a relatively clean bill of health throughout the rest of the squad. Atletico's Diego Godin has been ruled out with a thigh injury but the Spanish side will have Jan Oblak back from a shoulder injury.