Nyon - European champions Inter Milan will play Bayern Munich in a repeat of last season's final following the draw for the first knockout round of the Champions League on Friday.
Inter beat Bayern 2-0 in Madrid with two goals from Diego Milito to clinch their first European crown for 45 years but struggled in this season's group stage, qualifying for the last 16 as a runner-up. Bayern topped their group with five wins out of six.
The other stand-out tie paired this season's favourites Barcelona with Arsenal -- the team they beat 6-3 on aggregate in last season's quarter-finals.
Barcelona, who also beat Arsenal in the 2006 final, drew 2-2 in London last season before Lionel Messi demolished the Premier League side, scoring all four goals in Barca's 4-1 second leg win at the Nou Camp.
Real Madrid, the nine-times winners, face Olympique Lyon again after losing to the French side at the same stage last season.
Tottenham Hotspur will return to the San Siro to face AC Milan, after finishing ahead of Inter in the group phase.
In the other ties, AS Roma will play Shakhtar Donetsk of Ukraine, Valencia will play Schalke 04, Olympique Marseille face Manchester United and FC Copenhagen meet Chelsea.
First legs will be played on February 15 and 16 and February 22 and 23 with the return legs on March 8 and 9 and March 15 and 16. The final will be at Wembley Stadium on May 28.
Real Madrid are now coached by Jose Mourinho, the man who led Inter to the title last season, and they will relish a chance to atone for their mistakes of last term.
Last season Lyon won 1-0 in France before going through with a 1-1 draw in Madrid.
"We still have last year's elimination fresh in the memory," Real sporting director Miguel Pardeza told Gol Televison.
"It's curious to have them two years in succession. It should help us to learn and to make sure we don't make the same mistakes this time."
Tottenham, joint highest scorers in the group stage along with Arsenal with 18 goals, came from 4-0 down with a Gareth Bale hat-trick before losing 4-3 at the San Siro in October.
Darren Eales, Tottenham's director of football administration, said the club would take heart from that comeback when they meet the seven-times winners AC Milan.
"That second half and going into the home game gave the players the belief that they could compete with teams like Inter Milan and they showed it at White Hart Lane (where Spurs won 3-1)" Eales told Sky Sports News.
"As we've gone on in the competition we've grown in confidence and I think that's what the lads will take into the AC Milan game."
Last 16 Draw:
AS Roma (ITA) v Shakhtar Donetsk (UKR)
AC Milan (ITA) v Tottenham (ENG)
Valencia (ESP) v FC Schalke (GER)
Inter Milan (ITA) v Bayern Munich (GER)
Lyon (FRA) v Real Madrid (ESP)
Arsenal (ENG) v Barcelona (ESP)
Marseille (FRA) v Manchester United (ENG)
Copenhagen (DEN) v Chelsea (ENG)
First legs will take place on February 15-16 and 22-23, second legs on March 8-9 and 15-16