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.
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.
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.
Denmark's Odense also take a 1-0 advantage to 2006 semi-finalists Villarreal on Tuesday.
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.
