Monaco, quarter-finalists last season, must overturn a two-goal deficit at home to Valencia in arguably the most attractive of the week’s second leg clashes and Lazio defend a one-goal lead at Bayer Leverkusen.
With potentially millions of euros at stake, Tuesday and Wednesday’s matches promise unremitting theatre in contrast to the group stage itself which has become little more than a formality for Europe’s biggest clubs.
Five teams will be defending a one-goal lead away from home and two more, Valencia and Manchester United, will have a two-goal cushion to defend but with an away goal against them.
Only Dinamo Zagreb and Shakhtar Donetsk, who won away in last week’s first legs, appear to be in for a comfortable evening.
Astana will travel around 3,500 kilometres, a relatively short trip by their European standards, to defend a 1-0 lead on Wednesday against Cypriot champions APOEL Nicosia, surprise quarter-finalists in 2011/12.
“Astana’s victory doesn’t mean they have more of a chance of going through than we do,” said APOEL coach Domingos Paciencia. “We still have the game at home, where we will have our fans and good support.”
If Astana qualify, it could create logistical problems for their group stage opponents who would have to fly several thousand kilometres across five or six time zones to Central Asia for a midweek game.
Valencia, who have missed out on the group stage for the last two seasons, take a 3-1 lead to Monaco on Tuesday in a match which pits Portuguese coach Nuno Espirito Santo against his compatriot Leonardo Jardim.
Manchester United, for whom missing out on the group stage for a second season running would be unthinkable, lead by the same score as they visit Club Bruges on Wednesday.
Lazio, who visit Leverkusen and BATE Borisov, who travel to Partizan Belgrade, both have 1-0 leads to defend while Sporting Lisbon take a more vulnerable 2-1 advantage to CSKA Moscow and Celtic a 3-2 lead to Malmo.
Malmo are attempting to qualify for the second season running while Celtic want to avoid a repeat of last year’s dramatic playoff defeat by Maribor.
Defeat for Lazio, meanwhile, would mean that Serie A has only two group stage representatives for the second season in a row.
Dinamo Zagreb, who host Albanian champions Skenderbeu with a 2-1 lead already in the bag, and Shakhtar Donetsk, who won 1-0 away to Rapid Vienna last week, look clear favourites to progress.
Maccabi Tel Aviv are well-placed to spring an upset after holding Swiss champions FC Basel 2-2 away in the first leg.
Revenge would be sweet for Maccabi, who were knocked out of both the Champions League and later the Europa League by Basel two seasons ago and then saw the Swiss swoop for their coach Paulo Sousa.
(Writing by Brian Homewood, editing by Mark Meadows)