Real Madrid and Bayern Munich have one foot in the Champions League last four as they go into this week's quarter-final second legs while Barcelona face a harder fight for their berth with doubts over the availability of injured Lionel Messi.
With Real holding a comfortable 3-0 lead over Galatasaray before Tuesday's trip to Istanbul and Bayern travelling to Juventus with a 2-0 advantage on Wednesday, two semi-final spots seem already taken.
The other ties are much more delicately balanced with competition favourites Barca locked at 2-2 before hosting Paris St Germain on Wednesday and Borussia Dortmund tied at 0-0 before entertaining debutants Malaga on Tuesday.
The goals and magic of World Player of the Year Messi would usually be enough to dig Barca out of any sticky situation - as they did against AC Milan in the previous round - but if the Argentine does not play the team will need a different approach.
Messi sat out Saturday's 5-0 win at home to Real Mallorca in La Liga with a hamstring problem, the first league game he has missed through injury since the 2010-11 season.
He had physiotherapy and did some fitness work on Sunday but it was unclear whether he would be fit to face PSG.
Barca, though, still have reason for optimism that they can reach a sixth successive Champions League semi-final as Messi's stand-in against Mallorca, Cesc Fabregas, netted a hat-trick and coach Tito Vilanova was back on the bench after cancer treatment.
They are in good spirits after the return to competitive action of defender Eric Abidal following a liver transplant, while they remain 13 points clear of Real at the top of La Liga and have not lost at home in Europe for more than three years.
"There is life beyond Messi," Barca wrote on their website (http://www.fcbarcelona.es). "Maybe it's not as beautiful, but it exists."
Qatari-backed PSG geared up for the Barca trip by fielding a largely reserve team in a 2-0 win at Stade Rennes that restored a seven-point lead at the top of Ligue 1.
Brazil centre back Thiago Silva is a doubt because of a knee injury he sustained in the first leg, while holding midfielder Blaise Matuidi is suspended and could be replaced by Clement Chantome, who could feature alongside David Beckham.
There could be three Spanish sides in the last four as Malaga enjoy a dream run in their first season in Europe's elite club competition.
There has never been a tie that has ended 0-0 after two legs since the Champions League format began in 1992-93 and Malaga know any away goals they score at Dortmund could be key.
Malaga's preparations for the game have been far from ideal, though, with the death of coach Manuel Pellegrini's father, a 4-2 defeat at Real Sociedad in La Liga on Saturday and the team's plane being hit by lightning on the way to that match.
Fellow La Liga side Real Madrid enjoyed a far better warm-up to their second leg at Galatasaray, thumping Levante 5-1 in the league on Saturday despite having rested several first-choice players.
First-leg goals from Cristiano Ronaldo, Karim Benzema and Gonzalo Higuain have put nine-times European champions Real within grasp of a 24th semi-final appearance although they are not getting carried away.
"It's a tough match and our passage to the next round is not yet assured. Three goals is a big lead but we have to go there and play and at least get one goal," Ronaldo told reporters.
Centre back Sergio Ramos and midfielder Xabi Alonso are suspended for Tuesday's game at the Turkish side, who have won once at home in this season's competition and have reached the semi-finals only once, in 1988/89.
Newly crowned German champions Bayern Munich are in a similarly comfortable position after David Alaba scored inside 30 seconds before Thomas Mueller added a second in their first leg at home to Juventus last week.
Last season's losing finalists, who are looking for a third semi-final appearance in four seasons, secured their 23rd German league title in record time on Saturday by winning 1-0 at Eintracht Frankfurt.
Juventus, however, will take some hope from the fact that they have won all five European quarter-finals they have played against German opponents.