Liverpool, Arsenal and Rangers begin their UEFA Champions League group stage campaigns, while champions Barcelona tackle Inter Milan.
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Rafa Benitez's Liverpool welcome Hungarian champions Debrecen to Anfield determined to make a winning start against the group
stage newcomers with a sixth European success the target.
The visitors are in fine form domestically, but have unhappy memories of their previous meeting against English opponents, having suffered a 6-0 aggregate defeat at the hands of Manchester United in the third qualifying round in 2005.
Wednesday night's other fixture in Group E sees French champions Lyon up against Italian outfit Fiorentina, with rival managers Claude Puel and Cesare Prandelli expected to be battling it out with Benitez for the two qualifying berths.
All eyes will be on Arsenal striker Eduardo when the Gunners travel to Belgium to tackle Standard Liege after Uefa's shock decision to drop the Croatia international's two-match suspension for diving on appeal.
The Gunners' encounter against opponents who ran Liverpool close and defeated Everton in Europe last term will also see back-up goalkeeper Vito Mannone donning the gloves due to illness and injury sidelining Manuel Almunia and Lukasz Fabianski.
NegotiateAt first glance Group H appears to be the most straightforward to negotiate, but Greek giants Olympiakos and Dutch champions AZ Alkmaar, who meet in Athens, should not be underestimated.
The hosts, who have not won their opening group stage game in four attempts, parted company with coach Temuri Ketsbaia on Tuesday, with Bozidar Bandovic handed the reins.
Rangers' return to the continent's top table sees them make the tough trip to Germany to tackle a Stuttgart side who they were up against during the 2007 group stage, with victory at Ibrox followed by defeat at the home of the Bundesliga club.
Walters Smith's men hold realistic ambitions of progressing to the knockout stage of this season's tournament with Group G completed by Sevilla and Romanian newcomers Unirea Urziceni, who clash in Spain on Wednesday night.
Reigning champions Barcelona begin the defence of their trophy away to an Inter Milan side who have been unable to transfer their domestic dominance to Europe's biggest stage in recent seasons.
The match marks an immediate return to the San Siro for former Inter striker Zlatan Ibrahimovic while Samuel Eto'o, who opened the scoring for Barca in their May success over Manchester United in Rome, now wears the colours of the Italian club.
The Eastern European encounter between Ukraine's Dynamo Kiev and Russian champions Rubin Kazan completes the Group F fixtures, with striker Andriy Shevchenko back with his former club following his summer switch from Chelsea.