Chelsea head to Turin to face Juventus, the Blues don't have a great track record in Italy. And Cristiano Ronaldo can break yet another record if he plays for Manchester United against Villarreal.
Here's a look at the major stories around tonight's matches.
Juventus v Chelsea
Juventus won their season curtain-raiser against Malmo 3-0, but they will face a far sterner challenge in last season's European champions Chelsea.
Chelsea have only lost three of their last 32 Champions League group stages, losing none of their last 12 at group stage level and with Thomas Tuchel's incredible win ratio (68%), the Blues will be looking to stay undefeated.
However, Chelsea have lost each of their last four away games against Italian opposition in the competition.
Each defeat coming against a different side - Inter in 2009-10, Napoli in 2011-12, Juventus in 2012-13 and Roma in 2017-18.
There is no doubt that we are set to witness a great clash in Turin.
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Manchester United v Villarreal
Manchester United will be seeking revenge after Villarreal snatched the Europa League title last season in an intense penalty shoot-out.
However it won't be an easy ride for Ole Gunnar Solskjaer's side as they endured a disappointing defeat by Young Boys in the opening week.
And that loss to Aston Villa on the weekend means the pressure is creeping up on the Norwegian boss.
Villareall manager, Unai Emery, will be hoping to orchestrate another victory over the Red Devils and rightly so as the Spanish side are unbeaten in their last 16 major European games, the longest run of any side!
But the four Champions League clashes between Manchester United and Villarreal have all finished 0-0, making it the most played fixture in the history of the competition to see no goals scored.
And Cristiano Ronaldo will be looking to break Iker Casillas' record for the most Champions League appearances, setting a new record of 178 games.