This time the French club are the ones who have to travel with the winner meeting either Northampton Saints or Perpignan in the 16th Heineken Cup final at the Millennium Stadium three weeks later.
"We know each other pretty well after all those times we have played them in the Heineken Cup," said Irish international prop Cian Healy, a try scorer in the 20-8 away win over Aironi at the weekend that cemented their second place in the Magners League.
"Potentially this could be our final game in the Heineken Cup this season so it will be a clear case of 'do or die,' there can be no holding back."
The two teams have had some classic encounters - with perhaps Leinster's sensational 41-35 quarter-final win at Toulouse in 2006 the pick of the lot.
"I was still at school when that one was played, in fact it was the year that I was in the Belvedere College side that won the Schools Senior Cup," said 23-year-old Healy.
"I did play in last season's semi-final against them over in France and, while it is always great and enjoyable to play in those important games, you cannot enjoy it if you walk off without the win and we walked off without the win that would have put us in the final."
Healy has featured in Leinster's last 27 Heineken Cup matches since making his tournament debut in the Round 4 match against Edinburgh in December, 2008, and will relish returning to the Aviva Stadium after scoring two tries in the Pool 2 fixture against ASM Clermont Auvergne just over four months ago and being a key part of the team who beat Leicester Tigers 17-10 in the quarter-finals at the home of Irish rugby earlier this month.
"It is great to be going back the Aviva, we are turning it into a type of fortress, and the support we get there from the Leinster fans is unbelievable," he said.
"They are there for us every game, big or small, and it will be great to have them behind us for the semi-final.
"The semi-final is an enormous game for us. We certainly know Toulouse are very strong up front, are a well drilled side and have quality throughout but we will focus on what we can and must do and not on what they can do.
"This will be our fifth match against French opposition this season as we played Clermont and Racing Metro in the group stages and those games confirmed that part of the way French clubs play can be their unpredictability and how they can come up with different ways to play and win.
"We are playing well and putting few things together and, while there are also a few things to work on, we feel we are going in the right direction under Joe (Schmidt) who is certainly getting the best out of the players."