Castres face Montpellier in a potentially explosive rematch of last year's play-off while Racing-Métro clash with Toulon for a place in the final four.
With table toppers Toulouse and Clermont waiting in the semi-finals - which will be played at neutral venues - it's all or nothing this weekend as Castres look to reach the semis for the first time since 2001 while Toulon have their second crack at silverware this season.
Friday, May 25: Castres v Montpellier
Saturday, May 26: Toulon v Racing-Métro
Toulouse v Castres/Montpellier
Clermont v Toulon/Racing-Métro
Castres Olympique v Montpellier HR
Stade Ernest Wallon, Toulouse
Castres will have revenge on their minds after they lost 18-17 at home to Montpellier at the same stage last year. It was CO's first home defeat of the season. Has that influenced the hosts' decision to move the play-off to Toulouse?
Irrespective of the venue, Castres will start as slight favourites, having beaten Montpellier twice this season already. But it is sure to be a close game as Montpol have continued to grow as a team since their surprise visit to the final last year.
Castres are unbeaten in their last four games while Montpellier are coming off a narrow loss to Toulouse, at the same venue, a fortnight ago.
With Montpellier having to field 19-year-old scrum-half Eric Escande due to injuries to both their senior nines, coach Fabien Galthié knows it will be a tough challenge for the youngster who has barely played since last November.
"I prefer not to talk too much about that, because they are going to target him," said Galthié.
"He has played around a dozen matches. We don't have a choice, that's how it is."
The pivotal battle is set to be up front where Castres have been impressive this season, inspired by former All Black Chris Masoe.
Aside from Masoe - who is joining Toulon next season - Castres will look to Romain Teulet to keep the scoreboard ticking along and banish memories of the 34-year-old's penalty miss two minutes from time in last year's clash.
Teulet, who holds the world record of points scored for the one club with 3,017 in his 11 years at the three-time French champions, is adamant that has not left its mark.
"It is not because of my penalty we lost, we just didn't run the game," said Teulet, who surprisingly has never been capped.
In team news, Castres have named Thierry Lacrampe at scrum-half ahead of Rory Kockott, who is joined on the bench by Fijian veteran Seremaia Bai.
Montpellier have named a their first-choice XV - apart from Escande at nine - after skipper Fulgence Ouedraogo and full-back Lucas Amorosino both passed fitness tests on Thursday.
Castres: 15 Romain Teulet, 14 Romain Martial, 13 Max Evans, 12 Romain Cabannes, 11 Marc Andreu, 10 Pierre Bernard, 9 Thierry Lacrampe , 8 Matemini Masoe, 7 Yannick Caballero , 6 Ibrahim Diarra, 5 Joe Tekori, 4 Matthias Rolland, 3 Luc Ducalcon, 2 Mathieu Bonello, 1 Yannick Forestier.
Replacements: 16 Marc Antoine Rallier, 17 Saimone Taumoepeau, 18 Rodrigo Capo Ortega, 19 Steve Malonga, 20 Rory Kockott, 21 Seremaia Bai, 22 Thomas Sanchou, 23 Karena Wihongi .
Montpellier: 15 Lucas Gonzales Amorosino, 14 Timoci Nagusa, 13 Thomas Combezou, 12 Santiago Fernandez, 11 Martin Bustos Moyano, 10 Francois Trinh-Duc, 9 Eric Escande, 8 Alex Tulou, 7 Mamuka Gorgodze, 6 Fulgence Ouedraogo, 5 Thibaut Privat , 4 Mickael De Marco, 3 Giorge Jgenti, 2 Agustin Creevy, 1 Juan Figallo.
Replacements: 16 Erasmus Jansen van Vuuren, 17 Naama Leleimalefaga, 18 Hendrikus Hancke, 19 Alikisio Fakate, 20 Remy Martin, 21 Paul Bosch, 22 Pierre Berard, 23 Maximiliano Bustos.
Previous results Castres won 21-16 in Montpellier & 27-18 at home
Prediction: It'll be close, but Castres could have the edge. Castres by less than five points.
Kick-off: 21.00 (20.00 GMT)
Referee: Patrick Pechambert
RC Toulon v Racing-Métro 92
Stade Felix Mayol, Toulon
Saturday's second play-off sees two clubs with similar ambitions and histories face off. Racing won promotion to the top division one year after Toulon thanks largely - like RCT - to the multimillion Euro investment of a single man.
Since 2009, both clubs have made no secret of the ambitions to add the Top 14 title to their Pro D2 wins, steadily working their way up the hierarchy. Both are now rightly considered as legitimate contenders for Toulouse's crown.
Racing came close last year, losing out to Clermont in the semi-finals in similar fashion to Toulon the year before.
Toulon will start as favourites to advance to the last four this time having won both league games between these teams this season. More importantly, Toulon have not lost at home since September.
Racing will travel south with a fair measure of confidence however. Les Franciliens have won in Toulon three times in their last five visits, although two of those wins came in the second division.
Toulon have also been less than convincing in the recent outings, losing to relegated Brive and Agen before being held to a draw at home by Castres and stuttering past Lyon.
Toulon are also still smarting from defeat to Biarritz in last weekend's dismal Challenge Cup Final.
"We wanted to bring something back from London for all of us, for the club and for our incredible crowd. Toulon haven't won anything for 20 years but we are very ambitious," said English flank Steffon Armitage.
"I'm convinced we can bounce back - I'm sure about that. We have the qualities to finish the season well.
"Sometimes you must lose games to improve. It's a huge disappointment to lose the final but I am convinced we will perform better against Racing Metro and rewrite the history books for Toulon.
"Since Sunday we have been fully focused on Racing Metro. We have the opportunity to put the defeat behind us. The play off game in the Mayol is a huge game for us. It's a chance for us to bounce back and we'll be ready."
Racing have had a turbulent season off the field that has had a significant impact on their results. But their form in recent weeks suggests they've put their troubles behind them.
"We were staring into the abyss earlier this year and the positive thing is that we have moved forward from that," said centre Henry Chavancy, who is favoured to make the France squad for the Tour of Argentina in June.
"We have nothing to lose against Toulon. Everyone sees Toulon as favourites ..... all the better."
In team news, Toulon are sweating over the fitness of French international wing Alexis Palisson and hooker Sébastien Bruno. They are also waiting on a verdict in prop Carl Hayman's disciplinary hearing after being cited for a tip tackle against Biarritz.
Good news for RCT fans is that Bakkies Botha, Simon Shaw and Juan Martin Fernandez Lobbe have all passed fitness tests.
For Racing, injured wing Benjamin Fall has recovered in time to take his place in the squad but Springbok back Frans Steyn has been ruled out.
Forwards: Battut, Ben Arous, Bianchin, Brugnaut, Cronje, Dellape, Galindo, Ghezal, Leo'o, Le Roux, Nallet, Noirot, Sa, Tuugahala, Van der Merwe.
Backs: Chavancy, Descons, Estebanez, Fall, Germain, Hernandez, Imhoff, Lorée, Steyn, Vakatawa, Wisniewski
Forwards: Armitage, Botha, Bruno, Chilachava, Emmanuelli, Fernandez Lobbe, Gunther, Hayman, Ivaldi, Kubriashvili, Lewis Roberts, Samson, Shaw, Suta, Van Niekerk
Backs: Bastareaud, Cibray, Giteau, Lapeyre, Loamanu, Messina, Palisson, Rooney, Smith, Tillous-Borde, Wilkinson
Previous results: Toulon won 16-9 in Paris & 32-20 at home
Prediction: Toulons home record is very impressive. Toulon by eight points.
Kick-off: 21.00 (20.00 GMT)
Referee: Mathieu Raynal