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Clermont and Toulon have never won the European Cup, let alone reached the final, but the French heavyweights will bid to make it the fourth all-French final when they play Munster and Saracens respectively in the semi-finals.
Both are also favoured to meet in the French title final on June 1 but for the moment their priority is to seal their places in the final of European club rugby's most prestigious competition in Dublin on May 18.
Barring their way, though, are two formidable outfits.
Irish province Munster, the only one of the four to have won the trophy, have defied critics who wrote them off as being too old and instead drawn on all the experience that has brought them two European crowns to reach this stage.
Their win over Harlequins in the quarter-finals was indicative of their ability to overcome the odds and kept alive Irish hopes of capturing their sixth European Cup in eight editions.
Saracens, who lead their own championship, will host Toulon at English rugby headquarters Twickenham on Sunday and will be a fascinating tussle between present and past English fly-halves, as present incumbent Owen Farrell lines up for Saracens while the legendary Jonny Wilkinson starts for Toulon.
Clermont and Munster's clash on Saturday promises to be an explosive encounter with the French side stirring up the atmosphere by querying whether veteran Irish lock Paul O'Connell should be lining-up at all.
O'Connell -- who only returned to action recently after a long injury absence -- is judged by many fortunate to not be serving a long suspension after mistaking Leinster's David Kearney's head for the ball in a Celtic League match.
Kearney spent the night in hospital as a result but the 33-year-old O'Connell was not cited, which has left Clermont players scratching their heads at the decision.
"I have the impression that not all of us are judged by the same standards," Clermont flanker Julien Bonnaire said.
"There are some players who would have received 10 weeks' suspension for the same offence."
Part of the bitterness stems from memories of a group match in 2008 when Clermont's Jamie Cudmore received a five-week suspension for trading blows with O'Connell while the Irishman was simply yellow-carded.
Nevertheless the Clermont side are such a finely-honed professional unit under long-time New Zealander coach Vern Cotter that any animosity will be channelled into positive energy on the pitch.
"It is an intelligent squad which has experience and the habit of being together for some time now. I am almost superfluous," said Cotter.
"It is a squad that is pretty much autonomous and I am more or less a spectator these days. I arrive in the morning and all I do is drink coffee," he added with a twinkle in his eye.
Players such as scrum-half Morgan Parra and dazzling centre Wesley Fofana -- one of the few French players to emerge from the Six Nations with their reputations enhanced -- are just two of the potential match winners that Munster will have to cope with.
Munster's great domestic rivals and two-time defending champions Leinster came off second best to Clermont twice in the pool stage but Munster coach Rob Penney believes they are not unbeatable.
"Even when you're facing a large team like Clermont, every team has a vulnerability," he said.
"That's what we're trying to get across with this group. They'll give us opportunities but we'll have to take the opportunities when they're provided."
Saracens may be banking on having the vast majority of the spectators behind them but Toulon flanker Steffon Armitage -- who had two seasons at the English club -- believes that Wilkinson can teach Farrell, who has admitted the veteran kicker was his idol, a lesson.
"You can see Jonny is back to his best. He is putting his body on the line in training every day," said 27-year-old Armitage.
"I still think he has a lot more to offer. He is still playing 80 minutes week in and week out and putting his body on the line. I just think he is awesome.
"He brings a lot of belief and what Toulon should be is Jonny."
Fixtures (kick-offs GMT)
At Montpellier, France
Clermont (FRA) v Munster (IRL)
Saracens (ENG) v Toulon (FRA)