Barcelona are out to complete a revenge victory over Chelsea, holders Liverpool face elimination by Benfica and AC Milan tangle with Bayern Munich when Champions League action returns this week.
A place in the quarter-finals is up for grabs in the knockout round's second leg ties and none is more eagerly awaited than Barca's game with Chelsea at the Nou Camp.
Barcelona, who were knocked out by Chelsea over two acrimonious legs at the same stage last season, are in the driving seat this time after winning 2-1 at Stamford Bridge.
But the tone of the bitter rivalry was set within minutes of Chelsea's arrival at Barcelona airport on Sunday, with the London club's website reporting that their Portuguese manager Jose Mourinho had been spat at.
On the pitch, the threat from the hosts will again come from the likes of Brazil's Ronaldinho, Cameroon striker Samuel Eto'o and marauding Argentine prodigy Lionel Messi.
All three will look to get behind the defence of a Chelsea side with little option but to push forward and try to score at least twice to qualify on Tuesday.
The away goals rule also puts a big responsibility on the shoulders of captain and central defender John Terry, who scored an own goal at the Bridge, to keep things tight at the back.
Left back Asier Del Horno and defensive midfielder Michael Essien are both suspended.
Liverpool can ill-afford to concede at Anfield on Wednesday when they try to turn around a 1-0 defeat at Benfica.
CAPTAIN'S CHALLENGE
It could take another captain's performance from Steven Gerrard to drive his men into the last eight against a Benfica side who knocked out Manchester United in the group stage.
Liverpool have hardly been prolific up front -- with four goals in their last six games -- and Saturday's 0-0 home draw with Charlton Athletic was not the ideal warm-up.
Milan, who were famously beaten by Liverpool on penalties after leading 3-0 at halftime in last season's final, have a tentative foot in the next round after earning a 1-1 draw in Munich.
A second half equaliser by Ukraine striker Andriy Shevchenko from the penalty spot makes Milan favourites at the San Siro -- which will host Inter's game against Ajax Amsterdam a week later.
Milan will want to finish the tie in style, though, and striker Filippo Inzaghi, who took his tally to seven goals in five Serie A games with a brace in Saturday's 3-0 win over Empoli, looks the man to do just that.
Wednesday's game is one of two Italo-German ties, with Juventus needing to overturn a last-gasp away defeat by Werder Bremen when they meet again at the Stadio Delle Alpi.
Juve coach Fabio Capello badly needs his two first-choice strikers Zlatan Ibrahimovic and David Trezeguet, who scored a late goal in the first leg, to overcome their injuries.
Arsenal may struggle to match their superb 1-0 victory at Real Madrid two weeks ago but their swashbuckling 4-0 win at Fulham on Saturday will have sent out all the right signals to the Highbury faithful.
Though their reputation is for attacking football, led up front by Thierry Henry, Arsenal would doubtless settle for the dullest of 0-0 draws in north London on Wednesday.
Real, though, can hardly play any worse and could be fired up by the prospect of their first European game since the resignation of president Florentino Perez, architect of the Galacticos policy.
Fellow Spaniards Villarreal take on Rangers after drawing 2-2 at Ibrox and PSV face an uphill task at French champions Olympique Lyon after losing 1-0 at home.
