Real Madrid will be aiming for a record 24th semi-final appearance, Barcelona is targeting a sixth straight semi-final appearance while Bayern Munich is looking for its third semi-final appearance in the last four years.
However, debutants Málaga as well as Galatasaray and Paris Saint-Germain, with just two semi-finals between them, are confident that they can cause the upset.
Here is a look at the four intriguing ties.
Paris Saint-Germain v FC Barcelona
PSG will hope lightning strikes twice when they take on Barcelona, having beating Barca in their sole previous UEFA Champions League quarter-final. Their run to the semi-finals in 1994/95 was the French club’s best showing, but they have a long way to go to match the record of Barça, for whom victory would secure a sixth consecutive semi-final.
Something will have to give in the Parc des Princes as the hosts’ 23-game unbeaten streak at home in Europe receives the ultimate test from a side who have not lost the away leg of a quarter-final since defeat at Panathinaikos in 2001/02.
However, their usually serene away form has been missing at times this season. With the Azulgrana having lost two of their four matches on their travels this term, at Celtic and AC Milan.
With both sides holding a comfortable cushion at the top of their domestic leagues, focus can turn solely to the battle for a semi-final slot, with Bayern the more familiar campaigner of late.
The Serie A outfit were last in the quarter-finals in 2006, whereas Bayern are making their fourth last-eight appearance in five seasons. Nonetheless Juventus have not lost on the road on the continent since 18 March 2010, so will be confident of getting a result to defend in Turin.
However, it was Bayern who emerged unscathed the last time the teams met, following up a 0-0 draw with a 4-1 win in Italy during the 2009/10 group stage.
Málaga v Borussia Dortmund
Joining the field as champions of Germany, Jürgen Klopp’s Dortmund;s side have already had to beat some major teams to get this far. They won a a group that contained Real Madrid, Manchester City and Ajax.
In contrast, few could have predicted the progress of Malaga who are undefeated at home in the Champions League this season, their 2-0 victory over FC Porto on 13 March sealing their passage to the quarters.
Dortmund, meanwhile, remain unbeaten in this term’s competition, though they have won just one of their four away matches, which include a 2-2 draw with Madrid where they were frustrated by Mesut Özil’s 89th-minute equaliser.
Real Madrid v Galatasaray
Ironically these two sides met 12 years ago to the day in the quarter-finals also, when Galatasaray came from behind to beat Real Madrid 3-2 in Istanbul, only to fall 3-0 in the second leg.
Yet having posted successive away victories against Cluj, Braga and Schalke this season, Gala will be be optimistic of taking something from Wednesday’s trip to the Bernabeu.
However, Madrid’s daunting home record should instil faith among their fans, having won 13, and lost one, of 16 European fixtures at the Santiago Bernabéu since coach José Mourinho’s appointment.
It is the time of the year when the stars shine, and the biggest stars play for Barcelona, Real Madrid, Bayern Munich and Borussia Dortmund, which is why I expect these four sides to advance to the semi-finals.