English clubs in danger of total wipeout
The Premier League has provided three of the four semi-finalists for each of the last three seasons but this year has already seen a much-needed levelling out, with six countries represented in the last eight for the first time since 1998/99.
United, missing injured England striker Wayne Rooney for Wednesday's game, have the record books against them as they attempt to overturn a 2-1 first-leg deficit against a Bayern Munich team which has grown in confidence during the season.
Injury-hit Arsenal must either win or pull off a high-scoring draw away to holders Barcelona on Tuesday after last week's thrilling 2-2 draw when they came from 2-0 down after being outplayed for much of the game.
In the other matches, Girondins Bordeaux, trailing 3-1 from the first leg, need to become the first team since 2004 to overturn a two-goal leg deficit in the competition's knockout stages when they host Olympique Lyon in an all-French tie.
Serie A champions Inter Milan defend a 1-0 lead on CSKA Moscow's artificial pitch, which coach Jose Mourinho nonchalantly described the surface as "child's play."
The contests are likely to make nervous viewing for a number of World Cup coaches after high profile injuries to England's Rooney, Spain's Cesc Fabregas and Frenchman William Gallas in last week's matches.
Arsenal pair Fabregas, with a cracked bone, and Gallas, with a calf injury, were ruled out for the rest of the domestic season and will be struggling to make the World Cup, which starts in South Africa on June 11.
Rooney suffered only minor ligament damage and is expected to return in three weeks, although it was still enough to provoke mass hysteria amongst the English media with South Africa just around the corner.
Although United famously beat Bayern Munich 2-1 in the 1999 Champions League final after scoring twice in the dying minutes, it was their only win against the Bavarians in eight meetings.
Alex Ferguson's team have also not beat a German team at home in three attempts in the Champions League knockout stages.
The two sides also had contrasting fortunes at the weekend.
Manchester United lost 2-1 at home to Chelsea and were knocked out off the top of the Premier League by their opponents while Bayern won 2-1 at Schalke 04 to replace their hosts as Bundesliga leaders.
"We have a chance to succeed in Manchester as we are always capable of scoring away from home," said coach Louis van Gaal, who hopes to have Dutch winger Arjen Robben back in the team after he missed the first leg through injury.
Barca, with problems of their own for the visit of Arsenal, are without central defensive pairing Carles Puyol and Gerard Pique through suspension and injured striker Zlatan Ibrahimovic, who scored of both their first leg goals.
But they can still turn to Lionel Messi who has scored 19 goals in his last 29 Champions League matches and, ominously, was not on target last week.
Lyon, who reached three successive quarter-finals between 2004 and 2006 and lost them all, will hope to go one better against the French champions, although coach Claude Puel is cautious.
"The second leg is open. I know how good they are," he said.
Whoever wins on Wednesday will become the first French semi-finalists since Monaco in 2004.
CSKA's chances of becoming the first Russian side to reach the Champions League semi-finals have not been helped by the absence of suspended midfielders Milos Krasic and Yevgeny Aldonin.
Mourinho, will be glad to have missed the worst of the Russian winter although CSKA's artificial pitch could be a headache on Tuesday.
"We know how we want to play there, aware of the difficulties regarding the opposition and the artificial pitch, which will be a first for everyone," Mourinho told Inter's in-house TV channel.
"But I was joking with some of the players before, thinking of how we used to play in the road when we were children.
"'If you can play in the road', I said, 'why can't you play on an artificial pitch too'?"