Champions League holders Barcelona will begin their title defence at home against AC Milan in Group H.
In any other season, this fixture could very well be the final of the competition itself, and both clubs will feel confident that the result will not affect their chances in the competition, given the relative weakness of BATE Borisov and Viktoria Plzen.
Milan will be looking to capitalise on Barcelona's growing injury list; they are without first-choice central defensive pair Carles Puyol and Gerard Pique, and summer signing Alexis Sanchez is out with a torn hamstring.
Elsewhere, Bundesliga champions Borussia Dortmund kick off their return to the Champions League against Arsenal at home in Group F.
Arsenal will miss manager Arsene Wenger as hes he is still serving his touchline ban, but they will still be hoping for a result against Dortmund, who have had a slow start to their domestic season so far, losing 2-1 at home to Hertha Berlin on Saturday, and currently languishing 11th in the Bundesliga with seven paltry points from five games.
There will be another English club playing a German side tonight as Bayer Leverkusen travel to Stamford Bridge to take on Chelsea in Group E.
Chelsea boss Andre Villas-Boas may not field his first-choice XI with Sunday's Barclays Premier League trip to Old Trafford on the horizon.
"You'll see some changes tomorrow [Tuesday]. Then we'll make wise decisions for Sunday," said Villas-Boas, whose big decision once again revolves around whether or not to select Fernando Torres.
Leverkusen will be looking on to capitalise on that fact and make Michael Ballack's return to his previous club a pleasant one.
In the other Group E match, Racing Genk play Valencia at home. Sergio Canales is primed to make his European debut for the Spanish club as they look to get some points in the bag before they take on Chelsea or Leverkusen.
In Group F, Olympiakos will play their first match of the season against Marseille after their first two scheduled league matches were postponed after their scheduled opponents, Kavala and Olympiacos Volou, were relegated to the fourth tier owing to match-fixing offences.
Marseille are still winless five matches into the new season with three draws and two defeats, hovering just above the relegation zone. They will have to up their game to get the points when they travel to Greece.
Cyproit champions APOEL host Zenit St Petersburg in Group G as they return to the competition for the first time in three years.
Zenit will be without Sergei Semak, as the star broke his metatarsal in July, but will welcome the return of Vladimir Bystrov, as he makes a return from knee ligament injury.
In the other Group G fixture, Porto will play Shakhtar Donetsk at home, their first European match after the departure of former coach Andre Villas-Boas.
Porto have won all four of their league games this season and are confident of taking on Donetsk, who will be equally confident of their chances after famously beating AS Roma home and away in the competition last season.
BATE Borisov travel to play Viktoria Plzen in the last Group H tie. There will be little but pride for both sides to play for in their fixtures, as both clubs will be aggrieved to have been grouped with both Barcelona and AC Milan, which could mean their European dreams are crushed before it even begins.
The Belarussians are becoming regulars in the competition, which could give them the edge, while Plzen will simply be sticking around and seeing what happens in the group, after having knocked out both Rosenborg and Copenhagen to make it thus far.