Last season's runners-up Juventus and 1999 winners Manchester United face shock Champions League exits on Tuesday unless they turn around their first knockout round ties.
Italian champions Juventus slumped to a 1-0 defeat at Deportivo Coruna in the first leg, while United lost 2-1 at Porto.
By contrast, United's premier league rivals Chelsea and French side Olympique Lyon need only to hold their nerves, after 1-0 wins at VfB Stuttgart and Real Sociedad, to reach the quarter-finals.
Juventus will have home advantage at the Stadio Delle Alpi, but coach Marcello Lippi's injury list includes France striker David Trezeguet and three defenders, while experienced midfielder Antonio Conte is suspended.
Lippi, though, believes his players can fight their way out of trouble and go all the way to the final in Gelsenkirchen, Germany on May 26.
"It's easy to have faith when things are going well," he told the club's website. "But it's times like these when it's really needed and I've never lost faith in this team.
"The players and I have no intention of giving up on the Champions League. We've been to the final many times before and we know what pleasure that brings. And we'll be trying to do the same again now."
United will be without suspended skipper Roy Keane, after he was red-carded for treading on Porto keeper Vitor Baia in the first leg, as they hope to make the most of their away goal.
"There's very little between the sides but you would have to think we'll improve dramatically from the first leg," manager Alex Ferguson told reporters.
"You have to be prepared for anything that can happen in a European game and the most important thing is we impose ourselves."
Big-spending Chelsea have made it clear they will not be sitting back on their first-leg lead against Stuttgart, with their goal quest at Stamford Bridge helped by the return of influential Irish playmaker Damien Duff.
Lyon's players stand to make club history if they reach the quarter-finals for the first time, but they must see off a tenacious Spanish side.
Lyon coach Paul Le Guen told the club's website: "Real SociedadĀ are a team who really get stuck in. They are going to fight to the very end and we'll have to show the same spirit we had in the away leg if we're not going to get caught out."