Arsenal have been drawn against Spanish champions Barcelona in the last 16 of the Champions League, with the first leg at the Emirates Stadium.
Tottenham also face a difficult task after being paired against AC Milan, with the first game at the San Siro.
Manchester United face French side Marseille, while Chelsea have been draw against Danish outfit FC Copenhagen.
Holders Inter Milan face German side Bayern Munich in a repeat of last year`s final.
Barcelona defeated Arsenal 2-1 in the 2006 final and won 6-3 on aggregate at the quarter-final stage of last season`s competition.
The Spanish side won the second leg at the Nou Camp 4-1, with Argentine Lionel Messi scoring all of the goals.
"It is a tough draw for us," said Gunners secretary David Miles.
"But given that Barcelona got the better of us last year we feel that the time is right and that we can turn the tables this time.
"Lionel Messi is obviously one of the quality players in Europe and manager Arsene Wenger will have done his homework. He is their main danger man."
Barcelona are currently top of the Spanish league and defeated El Clasico rivals Real Madrid 5-0
Tottenham have already travelled to the San Siro this season, where they lost 4-3 to Inter. The London club, playing in the competition for the first time, trailed 4-0 at the break before a sensational Gareth Bale hat-trick ensured a tight finish to the match.
"It is back to the San Siro," said Tottenham secretary Darren Eales. "Hopefully we can play like we did in the second half against Inter and not the first half.
"We will take confidence from the second half that we can compete with AC Milan. Gareth Bale has been in sensational form in the Champions League. We play attacking football and we do have a goal threat.
"Hopefully we will get an away goal and bring them back to White Hart Lane and sneak through."
Inter defeated Munich 2-0 in last season`s final, which was played in Madrid.
"It is a very interesting draw," said Bayern director Karl Hopfner: "It is a very interesting draw to meet them again so soon after last season`s final.
"We are looking forward to it but both of us have not started that well in the league or the Champions League."
Lyon face Real Madrid and will be hoping for a repeat of last year`s victory over their Spanish opponents at the same stage.
The French side won 2-1 on aggregate and chairman Jean-Michel Aulus said: "It will be a very different Real Madrid side this year and it will be a very difficult tie.
"They may want revenge for last year, when it was a great result for us."
