Eternal rivals Manchester United travel to Liverpool in the Europa League last 16, first leg on Thursday in a battle of English football's two most successful sides.
United have won the English title a record 20 times, twice more than Liverpool, but the Reds have the edge abroad, having been crowned European champions on five occasions to United's three.
The Anfield encounter will mark the first time the teams have faced off in European competition, with the two Premier League giants combining to lift 17 continental trophies.
"This is why I signed for such a big club, to look forward to nights like this," Liverpool defender Nathaniel Clyne told the club's website.
"Everyone's excited. Everyone loves to play European football so it's going to be exciting up against our rivals United.
"I think we owe them from the Premier League games, which we probably should have got more out of. We need to take it to them, especially in the first leg when we're at home."
Winning the Europa League appears the best chance for either side to compete in next season's Champions League, with both United and Liverpool languishing outside the top four in England.
The Red Devils won both Premier League meetings this season, following up a 3-1 win at Old Trafford in September with a 1-0 victory on Merseyside in the reverse fixture.
However, United's 1-0 defeat at West Brom on Sunday snapped a four-game winning run in all competitions for Louis van Gaal's side, and Michael Carrick said they can't afford to let that derail them ahead of the Liverpool showdown.
"It is a setback but there are some massive games around the corner. Things were looking good (last) week; we were on the up, everyone was so positive. This is a blow for us but we need to get back, ready for Thursday," he said.
In contrast, Jurgen Klopp's Liverpool have bounced back impressively from the heartache of their League Cup final defeat to Manchester City on penalties by thrashing the same opponents 3-0 three days later in the league before rallying to claim a 2-1 win at Crystal Palace on Sunday despite playing the last half-hour a man down.
Liverpool won the last of their three titles in this competition in its previous guise as the UEFA Cup in 2001, but United have never been beyond the quarter-finals of this tournament.
Spurs tackle Dortmund
Tottenham Hotspur, winners in 1972 and 1984, take on Bundesliga giants Borussia Dortmund in another intriguing last-16 tie that pits together two more genuine contenders.
Premier League title hopefuls Spurs lost ground on leaders Leicester City after a 2-2 draw at home to rivals Arsenal in Saturday's north London derby and will face a stern test of their credentials by a Dortmund side still within reach of Bayern Munich in Germany following a 0-0 stalemate in last weekend's 'Der Klassiker'.
"We will now focus on Dortmund, a massive game for us," said Toby Alderweireld, speaking to Tottenham's in-house television channel.
"Every game from now until the end is like a cup final and we have to give everything, like we always do."
Gary Neville's Valencia head to Athletic Bilbao in an all-Spanish tie, less than two weeks after the Basque outfit rolled over Thursday's visitors 3-0 at the Mestalla in La Liga.
Holders Sevilla continue their bid for a fifth title in the past decade away to Basel, whose St-Jakob Park will stage this year's final, with Villarreal, the fourth Spanish side left in the draw, at home to Bayer Leverkusen.
Former winners Shakhtar Donetsk and Anderlecht meet in Ukraine, with 1998 runners-up Lazio in action at Sparta Prague and Fenerbahce entertaining 2011 finalists Braga of Portugal.
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