The Tigers return for their eighth consecutive final at the home of English rugby with hopes of clinching a record 10th title, while Quins have the chance to make history by claiming their first Premiership final victory.
With just days to go until the highly anticipated clash, Sports Mole speaks to ESPN commentator and six-time Leicester Premiership champion Ben Kay about both teams' chances of glory.
Let's start with the teams - Who do you think could be the standout players for each side on Saturday?
"There's a big question mark over Toby Flood and whether he's going to be fit or not. Stuart Lancaster and Richard Cockerill had a disagreement about the level of information from the England camp of Toby's injury but by the sounds of it, it looks like he might well not be fit so it's a massive start again for George Ford.
"With his man of the match performance in the semi-final [against Saracens] he proved he could do it. He looked exceptional in terms of the delay he had on his pass to draw defenders on to him and create holes for the likes of Alesana Tuilagi, who scored that try, and I think that could be a massive factor for Leicester this weekend.
"The front row battle in the scrum is huge. At the beginning of the season Harlequins, who were playing brilliantly and winning all their games, their scrum was their only weak point. They've improved massively but it's obviously a huge strength for Leicester and an area that they'll look to get dominance in and sometimes it just gives them that ability to get little penalties that gets them three, six, nine points ahead and then the dynamic of the game changes.
"So that's a big area as well but if you look at the weather forecast it's meant to be a beautiful day. Both teams play really attacking rugby - they'll want to play at a very high tempo. So, you look at the players in the back three for both sides as well and particularly Mike Brown's counter-attacking for Harlequins up against the likes of [Horacio] Agulla for Leicester and Geordan Murphy and Alesana Tuilagi, so there's some great battles throughout the game really."
Following Chris Robshaw's fantastic regular season for Quins - Do you think he can play a big part on Saturday?
"Yeah I do, his leadership was exceptional particularly earlier on in the year when he had that disappointment of not going to the World Cup. He bounced back by playing the season of his life. He fully deserves to be England captain and I think his leadership will be very important and his drive to go forward.
"I'm not sure what the fitness is like of all the Leicester players, but back row-wise, if they do send Julian Salvi up against [Robshaw] they're both very inspirational players. The back row is one area where the selection will be very interesting - whether they keep Robshaw at no. 7 or move him over to no. 6 and put Luke Wallace at no. 7. There's little decisions to be made for the coaches and the medical staff that could be key to the outcome of the game."
Horacio Agulla and Alesana Tuilagi are expected to play their final game for the Tigers on Saturday. Do you think their impending departures will give them extra incentive to perform?
"I think so. [Horacio] Agulla has been on such a rich vain of form but I think he'll be on a high anyway and he'll want to make sure he goes out in that respect. It will certainly be a very emotional day for Alesana [Tuilagi] who has obviously had a huge amount of his life and rugby career as a Leicester Tiger and he won't want to leave without a medal and also having a big impact on the final. You look at some of the finals he played in over the years and what a key component he's been. Twickenham's obviously been a very happy stomping ground for him."
Looking at the run-in to the final - Leicester are arguably in better form due to their unbeaten record in the last six matches as well as their victory over Harlequins a few weeks ago - Do you think form matters in this case or can anything happen on the day?
"Anything can happen on the day. Leicester won't be trusting their form and Harlequins will be trying to put what happened on the Stoop out of their mind and I'm sure if you asked any of the players [they'd] honestly say that it doesn't make a difference - it's a one-off game, they've played well enough this season, they know they've got the performances.
"I think where it does matter is in the game. As the pressure levels rise, Harlequins haven't had as much exposure to finals as Leicester. But the question mark is if Harlequins do get ahead and Leicester pull a try back, which could almost be the worst case scenario for them because then they will start to question 'oh here we go again'.
"So, it's just the dynamic of the game - it will have a bearing at some point but equally it could mean that if Harlequins go points up this time, they realise that they wouldn't be able to just shut up shop and hope to defend the lead. They'd have to keep playing, so it could possibly work in their favour but I certainly think Leicester have the edge psychologically going into the final.
"One of the players I'm most impressed with is Harlequins' Mike Brown because he is just a never-say-die guy and he's also never satisfied with a performance so I'm sure that if they did get any points this time round he'd be having stern words with the guys to make sure that they didn't let it slip."
What do you think it would mean for Harlequins and the Premiership itself if they manage to get their first title win this weekend?
"Obviously its good to not have the same team winning every year because it shows that anyone has a chance going into the season. It raises the excitement levels. I think for the club itself it would show what massive strides they've made from their time when they were relegated. It would be quite a big pat on the back for Dean Richards for the foundations that he laid in that time and through to [director of rugby] Conor O'Shea, who's taken over and kicked on from where Dean left the club.
"They fully deserve to be in the final and no-one would begrudge them winning it because they've led all season and that's a really difficult spot to be in because it's much easier to be in second place chasing than to be the people at the top trying to fend you off. They've done a fantastic job to finish top and it's just how well they can deal with the pressures of knockout rugby, which to be fair, they didn't do particularly well in the semi-final [against Northampton Saints]. I thought they looked a little bit stifled but perhaps once they get over the fact that 'yeah, we've got to the final', it will bring out the best in them."
With Leicester losing in the final to Saracens last year. Do you think they will feel more pressure to win it this time around?
"I think in the back of your mind [it's] somewhere but I don't think you really think about that going into a final. I think even if they'd won last year they'd still feel the same pressure. It's more the fact that the players would think, 'I've been through all this season and it comes down to the last 80 minutes and if I lose it I've got to go through it all again. It's three months before I can even get my boots back on to put it right if we do lose'.
"No-one really remembers who comes second so that's the sort of pressure I think you deal with primarily but certainly I think that the likes of Richard Cockerill will feel under slightly more pressure but if you look at how boards must think, I think if you get into finals it's a one-off game. They've probably never admitted it but getting to a final, they know the coach has really done his job and then it's just how the players perform on the day."
Obviously you've been there many times during your playing career with the Tigers. What will be going through the players' minds on the day?
"There is a bit of nerves. For me they were when you wake up and you've got a long time and you've got to get all your food and your nutrition and your hydration done and its almost like you're feeling tired and it's when you actually are on the bus pulling up to the stadium that those nerves change to excitement. The feeling of nervousness and excitement physiologically is similar but it's just that switch that you flick in your brain to go 'wow, this is why I play the game'. When you arrive at the stadium it's the first time you feel you can actually do something to get ready for the game and get excited and you can start warming up and some of the adrenaline dissipates because of that and you get into a nice zone that you're ready to go out and play."
Finally, after considering everything, who do you personally think will be crowned champions?
"If I was a betting man and I was setting the odds as a bookmaker, you'd look at Leicester's previous experience and the experience levels within the team. You'd look at the form books running into the game. You'd look at the most recent fixture and you'd look at their performances in the semi-final in knockout rugby. I think Leicester have won all those little battles so Leicester has to be favourites but having said that, the favourites don't always win and I wouldn't be surprised - it wouldn't be a shock if Harlequins won the game on Saturday. If I had to put my money somewhere I'd put it on the team that's been playing the best rugby leading up to the final. As I said, there are some good characters in the Harlequins team that could certainly overcome that."
ESPN has exclusively live coverage of the Aviva Premiership Rugby Final between Quins and Leicester, on-air at 2pm on May 26. For the first time in the match's history, ESPN will also provide 3D television coverage of the Final.