There will be no all-Premiership Champions League quarter-final after the three remaining English sides were kept apart in today's draw, though a repeat of the 2005 semi-final between Chelsea and Liverpool is a strong possibility.
Premiership champions Chelsea will face Valencia over two legs, while Liverpool will face group opponents PSV Eindhoven, who knocked Arsenal out in the second round.
Manchester United will have to overcome Roma and if they do so would face the winners of Bayern Munich and AC Milan for a place in the final in Athens on May 23rd.
Both United and Liverpool have the advantage of playing the second leg of their quarter-finals at home.
Chelsea chief executive Peter Kenyon was relieved that the club do not face English opposition in the last eight.
He told Sky Sports News: "The draw keeps the English teams away from each other until the next round. It's good for the teams in it and for the competition.
"I guess the only thing you would say is you would rather be at home in the second leg but at this stage you've got to go with the draw. Overall we're happy with the draw.
"This is a big competition, we've done well in it but never got to the final. The team is doing well and if you look at the teams in it at this stage we stand a good chance."
It is only the second time United have made it into the quarter-finals since winning the trophy in 1999 and United chief executive David Gill admitted the club had under-performed in Europe in recent years.
Gill said: "It's a fantastic draw. We haven't been in the quarter-finals for a few years and to be back is fantastic.
"For me, playing in Europe is about playing other European teams. Obviously Chelsea and Liverpool could meet in the semi-final and it could be an all-England final, who knows?
United boss Sir Alex Ferguson said: "We have never played Roma before, so it is new. That is the great excitement in Europe. You play teams you have never played before."
Ferguson fancied Lyon as dark horses to win the tournament this year and was therefore impressed that Roma knocked them out in the last 16 round.
"We respect their last result. They have some great players like De Rossi and Mancini.
"Obviously we do not look beyond this game. We must concentrate on this game and we are looking forward to it."
Liverpool secretary Bryce Morrison said he believed the feeling that ran through the club two years ago when manager Rafael Benitez guided the team to victory in the final in Istanbul was returning.
"We are just beginning to get it now and hopefully we can go all the way," he said. "I think it was a better draw for us with the teams which were remaining."
Liverpool have already beaten PSV 2-0 at Anfield in the group stages this season, while they held them to a scoreless draw in Eindhoven.
Asked to look ahead to the potential semi-final opponents for Morrison added: "It would be fantastic if we could get through the quarter-final.
"We had a great night at Anfield two years ago against Chelsea, or it could be Valencia, Rafa's previous team."
The last-eight first legs will be played on April 3rd and 4th and the return matches on April 10th and 11th. Semi-finals will be played on April 24th and 25th and the second legs on May 1st and 2nd.
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