Spanish giant Real Madrid looks to end its Champions League last-16 jinx when Lyon visits the Santiago Bernabeu while defending champion Inter Milan will hope Bayern Munich has peaked too early ahead of their second leg in Germany.
Madrid, a nine-time European champion, hasn't qualified for the quarterfinals since 2004 but Jose Mourinho's side is on course to halt that unwanted streak on Wednesday after drawing 1-1 in Lyon in the first leg.
Inter, the club Mourinho led to Champions League glory last year, is in a much more difficult position following a 1-0 loss to Bayern at home three weeks ago.
Bayern, looking to complete the job and gain revenge for its 2-0 defeat to the Italians in the 2010 final in Madrid, warmed up for Tuesday's second leg by thrashing Hamburger SV 6-0 on Saturday.
In the other two second-leg matches in the last 16 of Europe's elite club competition, English sides Chelsea and Manchester United will fancy their chances of qualification having done the hard work away from home.
Chelsea leads 2-0 against Danish team FC Copenhagen from the first leg while United, which is still on course for the triple trophy haul of Premier League, FA Cup and Champions League, is level at 0-0 against Marseille going into the return match at Old Trafford on Tuesday.
Madrid's home form has been stellar this season - the team has won all 22 matches at the Bernabeu - but it will be wary having been knocked out of the Champions League last year by Lyon at this stage.
"On Wednesday, we are going to have a difficult game and we have to be at our best," said Mourinho, who also won the competition with FC Porto in 2004. "Lyon is very good and what happened last year can help them psychologically.
"We can play 11 against 12 - and this 12th man is the Bernabeu."
Star forward Cristiano Ronaldo has missed the last two matches with a leg injury but the Portugal international, who is level with Barcelona's Lionel Messi on 27 goals in the Spanish league, could return for Madrid for the second leg.
"I hope he plays, but now he is not 100 percent and I don't like players who are not 100 percent," Mourinho said of his countryman.
In Ronaldo's recent absence, former Lyon striker Karim Benzema has impressed, scoring braces in the last three league matches.
Lyon, a team with pedigree in the Champions League knockout stages, has lost just once in the French league since the end of September.
Inter, the last Serie A team remaining in European competition this season after defeats for AC Milan and Roma in the first knockout round last week, is attempting to salvage some Italian pride when it travels to Bayern. But Leonardo's side will be running into a team which found some welcome form on Saturday, ending a run of two straight defeats and a turbulent period for outgoing coach Louis van Gaal.
"It was a very important reaction," said France winger Franck Ribery, a scorer against Hamburg. "Six goals, that's great and it's also very important for Tuesday's game. But it's going to be a very dangerous game."
Inter, which was poor at the San Siro in the first leg, only drew 1-1 at Brescia on Friday to hinder its chances of caching Serie A leader Milan in the standings. Brazil center back Lucio was injured in that match and is doubtful.
Fernando Torres, Chelsea's record signing at 50 million pounds ($80 million), will look to get off the mark for his new club following his Jan. 31 signing from Liverpool when the Blues host Copenhagen.
Chelsea should have no problem advancing to the quarterfinals but United may be left to rue not scoring an away goal at the Stade Velodrome in its first leg against Marseille.
A 0-0 draw leaves the series intriguingly poised but United manager Alex Ferguson rested some key players in Saturday's 2-0 win over Arsenal in the FA Cup quarterfinals and the team is very strong at home.
"We have been pretty immense at Old Trafford all season," said young center back Chris Smalling, who is again set to fill in for the injured Rio Ferdinand alongside Nemanja Vidic for the Premier League leaders.
"So, while we were disappointed not to get that away goal we will approach our task full of confidence."
French champion Marseille has a doubt over the fitness of striker Andre-Pierre Gignac (ankle).
Barcelona, Tottenham, Schalke and Shakhtar Donetsk have already reached the last eight, ahead of the draw for the quarterfinals and semifinals in Nyon on Friday.
