The Werkself reached the final back in 2002, but have never won a Round of 16 tie in the competition's current format.
bundesliga.com previews the decisive return leg in the Spanish capital...
Leverkusen arrive in the Spanish capital knowing that a draw will be enough to take them through to the quarter-finals. Conceding an away goal would be catastrophic for the hosts, meanwhile, with Diego Simeone's men needing to win on the night by two clear goals to progress.
Portuguese midfielder Tiago (l.) and Uruguayan centre-back Diego Godin are both missing through suspension. Saul Niguez is recovering from a blow to the kidney that left him hospitalised after the first leg, but Koke is fit again after missing out last month. Left-back Guilherme Siqueira has been sidelined by a hamstring injury.
Turkish defender Ömer Toprak is available after serving a one-game ban following his red card against SL Benfica in the group stage. Bosnian centre-back Emir Spahic is a doubt with a knee injury, while Lars Bender (l.) has missed the last three games owing to a niggling ankle complaint, but could earn a start against Atletico.
A lot of the ball will be expected to go through French winger Antoine Griezmann (r.) at the Vicente Calderon. The 23-year-old was kept pretty quiet at the BayArena, but his ability to turn a game in one fell swoop should not be underestimated. He also has a near-telepathic understanding with former VfL Wolfsburg and FC Bayern München striker Mario Mandzukic.
Karim Bellarabi will assume a similar role for the visitors, Leverkusen's counter-attacking inclination seemingly tailor-made for the Germany international. The pacy 24-year-old needs no invitation to get at opposition defenders and, should the game get stretched, it'll only play into his hands.
Simeone (head coach): "[Leverkusen take a very direct approach to the game. They're good going forward and have a lot of pace in the final third. We didn't put them under enough pressure in the first leg and were unable to play the direct game we would have needed [to gain something]."
Roger Schmidt (head coach): “[Winning our last five games] has obviously helped our confidence a lot. When the referee gets the game going it doesn’t matter what the form tables show, however. It’s clear to us we need another special performance to progress.”
Atletico were held to a goalless draw by RCD Espanyol at the weekend, but have won 20 of their last 22 European matches on home turf, including all three in the group stage. Josip Drmic (c.) and Leverkusen are currently on a five-match winning run in all competitions and have lost just one of four away matches in Europe this term.
Hakan Calhanoglu scored the only goal of the game to deservedly settle last month's first leg in Leverkusen's favour. Prior to that, the clubs had played out two 1-1 draws in the group stage of the 2010/11 UEFA Europa League. The Werkself's overall record against Spanish sides reads: W3 D2 L9.
Atletico: Moya - Juanfran, Miranda, Gimenez, Ansaldi - Raul Garcia, Gabi, Koke, Arda Turan - Mandzukic, Griezmann
Leverkusen: Leno - Hilbert, Toprak, Spahic, Wendell - Castro, L. Bender - Bellarabi, Calhanoglu, Son - Drmic