Liverpool host big-spending Russian outfit Anzhi Makhachkala at Anfield in their Europa League group A clash tonight with the English Premier League side seeking to avoid making unwanted history.
A 3-2 defeat by Udinese in Merseyside on match day two leaves Brendan Rodgers' men staring at the possibility of consecutive home defeats in Europe for the first time in the club's existence.
Anzhi, thanks to the financial backing of wealthy owner Suleyman Kerimov, have started to flex their muscles this season, with Guus Hiddink guiding the Dagestan-based club to the top of the Russian Premier League.
Undefeated in eight European fixtures this season, they will pose a serious threat to a Liverpool side who only secured their first home Premier League win of the campaign last Saturday.
Raheem Sterling's first-half strike proved the difference in a 1-0 victory over struggling Reading, a goal that cemented his status as the club's second-youngest scorer behind Michael Owen and drew praise from his manager.
"The biggest thing is maintaining the hunger he's got now because he can be a really top player. It's a long way to go for him but at the moment he's been a revelation," said Rodgers. "I don't have any concerns about him at this moment. For him, right up until now, he's been brilliant."
Like his Liverpool counterpart, Newcastle manager Alan Pardew has also used the tournament as a chance to blood some of his less experienced players.
Northern Ireland defender Shane Ferguson received plaudits for an impressive display in the Magpies 3-0 defeat of Bordeaux last time out, and the 21-year-old lauded Pardew's handling of the younger members of the squad.
"The manager has been really good to me this season, giving me a lot of chances, and hopefully I'm taking them.
"[Pardew] has told the youngsters that there are a lot of games and if we work hard we'll have a chance to shine," said Ferguson.
The group D leaders welcome Club Brugge to St James' Park tonight and will aim to maintain their flawless record against Belgian opposition, having won on all six previous occasions.
Unlike predecessor Harry Redknapp, whose disdain for the Europa League was well documented, Tottenham boss Andre Villas-Boas has set winning the trophy he won two years ago at Porto as one of the north Londoners' ambitions for this season.
Spurs are looking for their first win after draws against Lazio and Panathinaikos and go to Maribor in Slovenia on the back of a painful 4-2 home defeat by Premier League leaders Chelsea.
Defender Steven Caulker admitted Saturday's result was a bitter pill to swallow but was confident of a positive response.
"The lads are down but we have three away games now with two cup games either side of Southampton, so we'll look to bounce back quickly," said the England under-21 international.
Defending champions Atletico Madrid will try to extend their 15-match winning streak in Europe when they host Portuguese side Academica, who haven't won a European match since 1969.