From Celtic vs Rangers to Barcelona vs Real Madrid, the two north west giants have had some memorable clashes in recent years and the pair meet on Sunday at Anfield in what is set to be a mouthwatering clash.
It's the Red Devils who firmly hold the bragging rights heading into the match. United have won three on the spin against Liverpool and Kopites will be desperate for their side to snatch victory and take back the claims.
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Both Liverpool and Man Utd aren't the forces they formerly were. Whereas the pair were Premier League heavyweights, who could beat any side they came up against, they've both struggled to put a string of results together over the past one-and-a-half campaigns.
In an unpredictable 2015/16 season, it's quite remarkable that both teams are still within a squeak of finishing in the top four come May.
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The Reds parted ways with Brendan Rodgers in October and brought in Jurgen Klopp following a slow start to the campaign. The Merseyside outfit are still very much in a transitional period but bringing in the eccentric German to Anfield has indeed been a positive move and he's brought a monumental amount of rapture and belief.
Klopp's words with the media are always a joy to listen to and his actions on the touchline are even more entertaining. The ex-Borussia Dortmund boss has passion beyond belief and that's why he's been embraced by Liverpool fans.
Klopp has said that it will take time for Liverpool to be challenging for the title but patience will be given to him. He's fine-tuning his side and the 48-year-old has a big 2016 ahead of him.
Van Gaal struggles
The same cannot be said for Louis van Gaal, however.
Although the Dutchman has a greater resume than Klopp, having captured La Liga, the Bundesliga and the European Cup, Van Gaal has almost every United fan on his back.
The Red Devils have never recovered following the retirement of Sir Alex Ferguson in 2013. David Moyes lasted little more than nine months and Van Gaal's position is also under serious threat.
United have won just two of their last nine Premier League matches, which included a defeat to the newly promoted Bournemouth. Old Trafford legends have been harsh critics of their former side, with Paul Scholes recently labelling United boring to watch.
The negative football being played by the Greater Manchester side has almost become unbearable for United fans; the reception Van Gaal got following their victory over Sheffield United in the FA Cup spoke a thousand words.
When United have tried to play exciting football, like they did on Tuesday away at Newcastle United, their defensive frailties become exposed.
Nail in coffin
Liverpool fans love nothing more than rubbing defeat in their rivals' nose and could yet again send another one of their managers packing.
It's what happened to Moyes just over two years ago. As Liverpool were on the title trail, inspired by the goals of Luis Suarez and Daniel Sturridge, United were on a steady decline.
Moyes did not get the full support of the squad he inherited, nor the board of the club who he left Everton for. Almost every football fan could see that United needed time and investment, but the Scot was not given it.
When the Reds travelled to Old Trafford in March, they were genuine title contenders, whereas United had fallen into a mid-table side. A Steven Gerrard double and a strike from Suarez meant Liverpool travelled back with a memorable victory.
Just under one month later, Moyes was departed of his duties.
Having managed city rivals Everton previously, Liverpool fans already had malice for Moyes and they likely felt no guilt in having him handed his P45 - many Kopites would have personally presented it to him on a plate if they were given the opportunity.
If the Reds can produce another similar result to what they did, it could be the end of Van Gaal. A win for Liverpool means they go level on points with United and in a prime position to plunge an effort on the wide open top four places.
Confidence will be high in the Reds' camp. They showed a resilient attitude to score a last minute equaliser mid-week against Arsenal and Klopp's teaching are beginning to click into place. Roberto Firmino will be desperate to continue his rich vein of form following his brace against the Gunners and solid performance at Stoke City in the League Cup.
No manager wants to see one of their fellow peers without a job but that's what happens in football. If Klopp puts the final nail in Van Gaal's coffin, he'll likely not lose any sleep in doing so - after all, it could be him next given the normalities in modern day football.
Does Van Gaal deserve to be sacked? Have YOUR say in the comment box below!