The first semi-final, on Friday 20 May (19:45) will pit table toppers Leinster against in-form Ulster at the RDS in Dublin, with the teams having met at the end of April in the regular season.
And while Ulster were victorious on that occasion in Belfast, head coach Les Kiss is expecting a completely different challenge this time around, particularly away from home.
He said: "For the last five or six weeks, we've been at the edge of it and we've had to win to get where we have to so that's been good prep for us ahead of probably the hardest away game you could play.
"That's one of the challenges, I've always looked at the big games, the semis as close to 50/50 but history says it's probably closer to 60/40 if you get the home advantage but that's one of the challenges you have to come against.
"We also know the last time we played them they were probably short a run, they will be a totally different beast."
Leinster sealed top spot in the table with a bonus-point victory over Benetton Treviso in their final game of the regular season, and as they prepare for a return to Dublin, second row Mike McCarthy wants to give the home fans a great show.
He said: "We wanted that for our fans to give them a home semi but now we need to go on and win that. It will be a very tough game for us after we had a very bad day at the office up at Ulster. They are playing great rugby, so we're under no illusions as to how tough it will be."
The second semi-final on Saturday 21 May (18:30) will see a rematch of the final game of the regular season as Connacht host defending champions Glasgow Warriors at the Sportsground in Galway.
And with the final taking place back in Scotland the following week, Glasgow head coach Gregor Townsend believes it's an exciting time for Scottish rugby.
"We're here to promote the Guinness PRO12 Final, it's fantastic for Scottish rugby that the final is being held at BT Murrayfield, it's great for the Guinness PRO12 that over 30,000 tickets have been sold," he said.
"For us it's about getting to the final wherever that might be. We know we've got a lot of work to do to play better and get a chance of making that final. But it's a great thing that so many tickets have been sold already."
Connacht will host a semi-final for the first time, but while they are the only team not to have previously won the competition, head coach Pat Lam is relishing the opportunity to play knock-out rugby.
He said: "It's play-off rugby now, we know that the other three teams have been there before and won it.
"This is new territory for us but the way we see it, there's a one in four chance. The biggest thing we've done throughout the season, we've worked hard to get it at home.
"There's no doubt it's pretty magic at the Sportsground. Both teams have shown throughout the season that they like to play a certain game which is entertaining so if we get the weather it will be a great day at the Sportsground."
In a season full of surprises in the league, where there was virtually nothing to choose between the top three right up until the final weekend, it makes it impossible to pick an overall winner.
And for Martin Anayi, managing director at PRO12 Rugby, that means there is all the more reason for all rugby fans to book their tickets to Edinburgh - no matter who you support.
"The Guinness PRO12 Final in Edinburgh will be a spectacular afternoon," he said. "We have four hugely talented teams that have reached the play-offs and all are worthy of gracing the final at Edinburgh.
"Just like the regular season, it's so difficult to call or predict who will lift the trophy in Edinburgh and that is what makes our competition so unique and so popular for supporters.
"Whether you support one of the four teams represented in the play-offs or you are just a rugby fan keen on soaking up a special atmosphere and occasion; Edinburgh will be the place for you on May 28."
To be part of a great weekend in Edinburgh, and to buy tickets, hospitality or for accommodation information for the Guinness PRO12 Final, 28 May at BT Murrayfield visit: www.pro12rugby.com