Jose Mourinho's Chelsea, one point shy of their second successive title, need to overcome familiar foes Liverpool on Saturday to keep alive their bid for a coveted league and FA Cup double.
The prize for the semi-final victors at Old Trafford will be a Millennium Stadium final on May 13 against Middlesbrough or West Ham who meet on Sunday at Villa Park.
It will be the 10th time in two seasons the English champions have met the European champions with Liverpool winning just once, at last year's Champions League semi-final home leg.
Rafael Benitez's men have secured three other draws in European competition against Chelsea but lost all four league games and last year's League Cup final.
After this season's Champions League disappointment for both sides, Europe's most prestigious domestic knockout trophy has assumed added importance.
"It's the most famous cup in the world," said Liverpool's Norwegian defender John Arne Riise. "Back in Norway it's a massive competition."
Liverpool, third in the league, have something to prove after trailing second-placed Manchester United who also lifted the League Cup.
Chelsea, backed by ambitious owner Roman Abramovich's billions, completed a league and League Cup double last season as well as reaching the Champions League semi-finals. Despite their Premier League dominance, a poorer showing this season would look like failure.
TWO TROPHIES
Frank Lampard, who has already beaten the Premier League record for goals by a midfielder with 16 and is looking for his 20th in all competitions on Saturday, said Chelsea were determined to secure both trophies.
"The aim is the double. We have...a huge game against a very good team in the semi-final and that will be a big battle. Our battle is on both fronts and we won't let up," he said.
The double has been won only 10 times in more than 120 years of competition, including by Liverpool in 1986.
Middlesbrough, who have never lifted the trophy, coming closest in 1997 when they were beaten by Chelsea in the final, could be distracted by other matters, however.
The West Ham game is sandwiched between two legs of their UEFA Cup semi-final with Steaua Bucharest and they travel to Villa Park three days after the tough trip to eastern Europe.
Without the strength in depth of Chelsea and Liverpool, manager Steve McClaren, who is being touted as successor to Sven Goran Eriksson as England manager, said he had used every fit player at the club "including the kids" in their last two games. "And we may have to do that again in the next few games."
Three-times former winners West Ham United, promoted this season and safe from relegation with only an outside chance of a UEFA spot from the Premier League, have little else on their plate.
With Chelsea and Liverpool having already secured Champions League spots next season an enticing UEFA Cup place beckons even for the FA Cup runners up.
Alan Pardew's Hammers will be anxious to forget the untimely 2-0 defeat they suffered at the Riverside last Monday preferring to remember their 2-1 win at home last October. On neutral ground it is too close to call.
