AC Milan, Inter, Barcelona and Manchester United will be looking to put one foot in the Champions League quarter-finals this week, as the world's top club competition returns from a winter break.
Though the second group phase is only reaching the halfway stage, several clubs will be hunting for a third consecutive win that would set them up nicely for a place in the last eight.
Nowhere is that more true than Group A, where the two clubs with six points, Inter Milan and Barcelona, meet at the Nou Camp, while Bayer Leverkusen and Newcastle United do battle in the hope of putting their first points on the board.
Barcelona, who won Saturday's Catalan derby with Espanyol 2-0, will have new boss Radomir Antic in charge after Dutchman Louis van Gaal left last month following a poor run of domestic form.
Barca had always sparkled for Van Gaal in Europe, though, and another victory for the hosts on Tuesday would set a new Champions League record of 11 successive wins.
Inter go into the game as Italy's joint league leaders despite conceding two penalties and being reduced to 10 men for the final hour of a 2-1 defeat by Chievo.
However, Leverkusen have had an even worse run-in after five straight defeats for last season's Champions League finalists resulted in Sunday's sacking of coach Klaus Toppmoeller.
A tough assignment for caretaker manager Thomas Hoerster, Tuesday will be a special moment for Newcastle manager Bobby Robson, who will be celebrating his 70th birthday.
ARSENAL'S CONFIDENCE
Group B also pitches the leaders against each other when Arsenal and Ajax Amsterdam, who have four points apiece, face each other in north London.
Arsenal's confidence will be sky high after their resounding 2-0 FA Cup victory at Manchester United on Saturday.
Better still, manager Arsene Wenger was able to rest Dutch playmaker Dennis Bergkamp and Brazil midfielder Gilberto, and use the English premier league's top scorer, Thierry Henry, as a late sub at Old Trafford.
Roma, whose 0-0 draw with Brescia on Saturday left them with just one win from their last six matches, will struggle to score their first points of the second phase at home to Valencia.
The Spaniards have so far drawn with Arsenal and Ajax, but the return of Argentine winger Kily Gonzalez from injury will improve their chances of a first win and they will be buoyed by Saturday's 2-0 league win over Malaga.
AC Milan's fine form this season should continue with a third consecutive victory in Group C when they host winless Lokomotiv Moscow at San Siro.
Milan missed their chance to join leaders Inter and Juventus at the top of Serie A when they were held to a 2-2 draw by Lazio on Sunday and remained third in the table.
Things will start to look pretty desperate in Group C for holders Real Madrid if they lose at home to Borussia Dortmund.
The Germans lie second on three points, while Real, who came into the tournament looking to win it for the 10th time, are bottom with just one point.
Sunday's 1-0 defeat at Osasuna, in which Luis Figo was sent off, was no way to prepare but Real's home advantage and European pedigree should enable them to turn things around.
Group D look set for a thriller at Old Trafford when leaders Manchester United take on old foes Juventus.
United famously came back from 2-0 down to beat Juventus 3-2 in Turin on their way to winning the 1999 Champions League and another win on Wednesday would give them nine points.
Though the FA Cup defeat will have dented team morale, Ferguson's side have plenty of character in adversity -- as Juventus already know to their cost.
Marcello Lippi's side, who are second on four points and would go top with a win, limbered up by joining Inter at the top of Serie A with a 2-1 win at Parma on Sunday.
Lippi will also be encouraged by one of those goals coming from Marco Di Vaio, the man who is replacing injured striker Alessandro Del Piero.
Deportivo, with one point so far, travel to face Basel -- the surprise package of the first group phase but who have been found out in the second with two heavy defeats.