Atletico Madrid, tough to beat on the road in the Champions League, pose a stern test for a Bayer Leverkusen side in poor form and with an equally poor record against Spanish clubs in Europe.
Last season's runners-up have lost one of their nine away games in the competition since September 2013, winning five of them, and will be confident of taking a positive result home from tonight's Round of 16 first leg.
They bounced back from a surprise defeat at Celta Vigo with a 3-0 success at Almeria in La Liga on Saturday that lifted the Spanish champions to within three points of second-placed Barcelona.
Diego Simeone's side rediscovered the intensity that had been missing in Galicia and forwards Mario Mandzukic and Antoine Griezmann showed their partnership could be the key to Atletico's hopes of silverware this term.
Mandzukic, who knows the Bundesliga well from his stint at Bayern Munich, converted a 13th-minute penalty and twice set up Griezmann to score before Atletico eased off in the second half. "The victory was very welcome after the defeat in Vigo," Simeone told a news conference.
Simeone is unlikely to have Koke available after the Spain midfielder sustained a hamstring injury in this month's 4-0 La Liga victory at home to Real Madrid.
The Argentine coach is also aware yellow cards could prove costly for Cristian Ansaldi, Gabi and Diego Godin, all a booking away from a suspension that would seem them miss the return leg.
For Leverkusen it is a different story with the German club having never won a last-16 tie, with the competition having a second group stage when they reached the final in 2002.
They have also been struggling in the Bundesliga with one win in their last six games.
But coach Roger Schmidt is confident the Champions League can help them rediscover their form from earlier this season. "The Champions League is the best thing there is," said Schmidt. "We are really looking forward to it and it will help us."