A fierce rivalry with consequences for both the title fight and the battle for the Champions League places.
Ole Gunnar Solskjaer demonstrated his tactical acumen yet again in Monday's 2-0 FA Cup victory away at Chelsea - and he's again likely to use his 'big game' system for this meeting with Jurgen Klopp's Liverpool.
False nine versus false nine?
Indeed, United's big game system is somewhat similar to the one used by Klopp: featuring two wide forwards going in behind, and a false nine dropping into slightly deeper positions. Solskjaer uses it as an alternative to a 4-3-3, and Klopp has reverted to it having used a 4-2-3-1 earlier in the campaign. This could be a clash of two similar systems.
The question, though, is precisely who plays in the front three for Manchester United. Jesse Lingard and Anthony Martial both limped off with muscle injuries against PSG ten days ago, and were expected to be out for between two and three weeks. However, some reports suggest they could be involved here, which would be a major boost to Solskjaer. Both know how to play their roles in this system perfectly
That said, their replacements didn't perform too badly against Chelsea. Juan Mata played the advanced midfield role well, nullifying Jorginho, while Romelu Lukaku often looks more comfortable out wide rather than upfront. Tactically, Lingard and Martial are a better fit, but Mata and Lukaku aren't back back-ups.
With Alexis Sanchez continuing to look out-of-sorts, Marcus Rashford will continue - probably on the right if Martial is fit, probably on the left if he's not.
Familiar defence and midfield for United
In deeper positions, Solskjaer has a clearly defined regular defence and midfield, which isn't something you could say about Jose Mourinho. David De Gea will play behind Ashley Young, Chris Smalling, Victor Lindelof and Luke Shaw.
Nemanja Matic will play the deepest midfield role, with Ander Herrera - who opened the scoring at Stamford Bridge - to his right. Paul Pogba will be handed freedom to push forward into attack, and is in excellent goalscoring form, making late runs and topping up his goalscoring tally with a fair few penalties.
Liverpool likely to use a 4-3-3
Klopp's front three will be comprised of Sadio Mane, Roberto Firmino and Mohamed Salah. Mane is in good goalscoring form in 2019, Firmino had a slight dip in form but has played well in recent weeks, while Salah was quiet in the 0-0 draw with Bayern but nevertheless starts as the favourite to open the scoring here. The shift back to 4-3-3 means Xherdan Shaqiri has dropped back down to the bench.
In midfield, however, there may be changes. The return of Virgil van Dijk means Fabinhoshould be free to shuffle forward into his favoured position in midfield, potentially displacing Jordan Henderson - although Liverpool's captain was impressive in midweek against Bayern. James Milner may hope to return here, although Naby Keita is in decent form and Georginio Wijnaldum has been excellent over the last couple of months. Expect Liverpool to start the game at a high tempo, and in terms of pressing they're at a more advanced level to Solskjaer's United.
Could Fabinho stay in defence?
Van Dijk's return is clearly a huge positive, although Fabinho was excellent in defence against Bayern. There's a chance he could continue there, with Joel Matip dropping out, although this remains unlikely.
The real key to this game, however, is the extent to which Liverpool's full-backs push forward. Both Andrew Robertson and Trent Alexander-Arnold have been excellent on the overlap this season and switch play between themselves excellently. But with United's wide forwards threatening to run in behind, this could also be Liverpool's area of weakness.
It's also worth considering the battle between goalkeepers. De Gea has been back to somewhere near his best in recent weeks, while Alisson will be keen to atone for his mistake in the reverse fixture, which ultimately didn't cost United.
I think this game could be tight, especially with both sides likely to deploy a similar system, packing the midfield zone - there might not be many possible out-balls.
Man United are currently in fourth place but just a point ahead of Chelsea and Arsenal and of course this is Liverpool’s game in hand and probably their hardest game left this season, a win here is huge, it would put them three points ahead of Man City and City still have to go to Old Trafford.
Jurgen Klopp’s men are rightly favourites trading around 2.46 but they would happily take a point now if offered. United are a team high on confidence and even though it will assist their local rivals, they would like nothing better than to severely dent the Reds' title charge.
Despite both teams playing well, Liverpool have only won one of their last three on the road and United haven’t managed to win either of their last two on home soil so it’s hard to be confident about either team claiming all three points.
Liverpool have only failed to score in one of their last nine league visits, however, they don’t have a great record here, their only win during that period was in 2014 (0-3).
Draw 1-1 in the Correct Score market at 7.4.
Over 2.5 goals at 2.00.