BERNE - Arsenal, with 13 consecutive Champions League appearances, and Olympique Lyon, with 11, are in danger of ending their long presence as they face difficult qualifying ties this week.
On the other hand, Viktoria Plzen, representing a city more famous for beer than football, are poised to qualify for the first time while Odense and Wisla Krakow could follow suit if they can defend narrow leads away from home.
Former champions Bayern Munich and Benfica, also involved in this week's 10 second leg ties in the fourth qualifying round, are well-placed to guarantee their places.
Arsenal will take a slender 1-0 lead to Udinese for Wednesday's match which could not have come at a worse time for Arsene Wenger's team.
Hit by injuries and the departure of midfielder Cesc Fabregas to Barcelona, Arsenal have taken only one point out of six in the Premier League but their poor domestic start would be nothing compared to missing out on the Champions League for the first time since 1997/98.
Udinese consider the Champions League as a bonus and sold key players Gokhan Inler and Alexis Sanchez as they decided to cash in on last season's impressive fourth place in Serie A.
Despite this, and not having played a competitive match this season, Udinese produced a slick performance in London last week.
Olympique Lyon have a two-goal cushion to take to Rubin Kazan after their 3-1 win last week although the Russians' away goal is cause for concern for the French side.
"We have an advantage but we're not through yet because anything can happen in the Champions League," said Lyon striker Bafetimbi Gomis, who scored in the first leg.
"Rubin have a good mentality, as well as being tough competitors. It'll be like a war over there so we'll need to make the most of our weapons."
Viktoria Plzen's 3-1 win away to FC Copenhagen last week has given them an excellent chance to qualify on Wednesday and put the city where Pilsener beer was developed in the 19th century on the football map as well.
Viktoria's squad is all-Czech apart from four players from neighbouring Slovakia.
Wisla Krakow, on the other hand, fielded only two Poles in their starting line-up last week in the 1-0 win at home to APOEL, who had only one Cypriot player.
The Polish team, who visit the Cypriots on Tuesday, have reached the final stage of the qualifiers for the seventh time, having lost on all six previous occasions.
Denmark's Odense also take a 1-0 advantage to 2006 semi-finalists Villarreal on Tuesday.
Four-times European champions Bayern Munich, whose Allianz Arena will host the final, will enjoy a 2-0 cushion at FC Zurich.
The Swiss League runners-up showed little last week to suggest they have what it takes to overturn the deficit in Tuesday's return at the Letzigrund, better known for staging the annual Weltklasse athletics meeting.
Benfica, who started with eight South Americans and no Portuguese players last week, are in the driving seat for the visit of Twente Enschede on Wednesday after last week's 2-2 draw in the Netherlands.
Twice European champions and five-times runners-up, Benfica have made a surprisingly modest six appearances in the Champions League.
In the other three ties, Dinamo Zagreb, Croatian champions for the last six seasons, take a 4-1 lead to former European Cup finalists Malmo on Tuesday and Sturm Graz start as favourites at home to Belarus side BATE Borisov on Wednesday after drawing 1-1 away last week.
Maccabi Haifa defend a 2-1 lead at Genk, where coach Frank Vercauteren has left since last week's first leg and to join United Arab Emirates outfit Al Jazira Club.
Pierre Denier and Hans Visser, Vercauteren's former assistants, will be in charge of the Belgian side in Tuesday's match.