For Manchester United, a win this weekend would all but guarantee them a third consecutive Premier League crown. They already sit seven points and a game in hand ahead of Liverpool and Chelsea, so three points against their North West rivals would all but decide the title race.
Funnily enough, the Red Devils began 2009 as outsiders on the domestic scene. Their sojourn in Japan for the Club World Cup - and the stuttering form of Luiz Felipe Scolari's Blues - allowed the men from Merseyside to gallop clear at the tabletop at the turn of the year.
But a run of 11 straight league wins since Boxing Day has seen United reclaim their perch at the summit of the standings. They will hope to continue that trend when they host the Reds on Saturday lunchtime, and none more so than Scouse striker Wayne Rooney.
"I grew up an Everton fan, my whole family are Everton fans and I grew up hating Liverpool – and that hasn't changed," the former Goodison Park hero said on Thursday.
"I think coming to Old Trafford will be a difficult game for them. They know they need to win, they need the three points. I'm sure they will be up for it and we certainly will be too.
"It will certainly end Liverpool's chances if we win and that's why we're looking forward to it."
United come into the clash in high spirits and surrounded by talk of a 'Quintuple' after their Champions League triumph over Inter, but their upcoming opponents should take even more confidence from their midweek exploits.
You wouldn't have known Liverpool were struggling for form if you watched their demolition of Real Madrid on Tuesday evening.
Having grabbed a 1-0 win in the first leg at the Santiago Bernabeu thanks to an air-tight defensive display, the Mersey giants then proceeded to put four unanswered goals past a helpless Iker Casillas in the return fixture, thus booking their sport in the quarter-finals.
However, as is so often the case with Rafael Benitez's side, their European efforts are in no way reflective of their domestic situation. For example, the impressive victory in Spain two weeks ago was followed up immediately by a disastrous 2-0 defeat at Middlesbrough. Many would would tipping a similarly sluggish showing at Old Trafford this weekend.
Liverpool haven't fared especially well in their arch-rivals' den over the past few years; in fact, the last time they returned with three points in league play was in 2004, when Danny Murphy was the hero. However, they are yet to lose against a Big Four opponent this term, and they will hope to replicate their 2-1 victory over Sir Alex Ferguson's champions at Anfield earlier in the campaign.
The Reds, who have won just three league games since their 5-1 mauling of Newcastle United at the end of December, are well aware that defeat against United would end their title chase once and for all. And Martin Skrtel has assured the Kopites that they will be going all-out for the win.
The Slovakian centre-half, who starred against Los Blancos, said recently, "Any result other than a win would mean a definite end to our title hopes.
"Despite the point difference, we are going into the match with the goal of winning. We will see if we can do it but, one thing is for sure, we are in a good mood after beating Real."
And as United would draw level with Liverpool on 18 English championships should they win this season, there is no lack of motivation for Benitez's boys.
FORM GUIDE
Manchester United
Mar 11 Man United 2-0 Inter (Champions League)
Mar 07 Fulham 0-4 Man United (FA Cup)
Mar 04 Newcastle 1-2 Man United (Premier League)
Mar 01 Man United *0-0 Tottenham (Carling Cup)
Feb 24 Inter 0-0 Man United (Champions League)
Liverpool
Mar 10 Liverpool 4-0 Real Madrid (Champions League)
Mar 03 Liverpool 2-0 Sunderland (Premier League)
Feb 28 Middlesbrough 2-0 Liverpool (Premier League)
Feb 25 Real Madrid 0-1 Liverpool (Champions League)
Feb 22 Liverpool 1-1 Manchester City (Premier League)
TEAM NEWS
Manchester United
Ferguson's defence remains light on personnel, with Gary Neville, Wes Brown and Rafael da Silva all sidelined, but Rio Ferdinand is expected to start after coming through Wednesday's win over the Nerazzurri unscathed. The very capable Jonny Evans will be on stand-by.
Rooney is likely to partner Dimitar Berbatov in attack, although Carlos Tevez - who scored at Anfield in October - may well feature in some capacity.
Possible XI: Van der Sar - O'Shea, Ferdinand, Vidic, Evra - Ronaldo, Carrick, Scholes, Giggs - Berbatov, Rooney
Liverpool
Albert Riera should return to the starting lineup after missing the midweek mauling of Madrid through suspension. Ryan Babel will most probably make way, despite a bright showing against the Merengues.
Danish defender Daniel Agger is still hampered by a back problem, but Yossi Benayoun - who hasn't played since scoring at the Bernabeu last month - is a chance to make the squad as he recovers from a hamstring problem.
Possible XI: Reina - Arbeloa, Carragher, Skrtel, Aurelio - Mascherano, Alonso - Kuyt, Gerrard, Riera - Torres
PLAYER TO WATCH
Manchester United
After his controversial comments during the week, all eyes will be on Wayne Rooney as he attempts to kill off Liverpool's title hopes. The 23-year-old is perhaps not in the finest form of his career, but everyone knows what the former Evertonian is capable of.
Liverpool
At the other end of the park, Fernando Torres will be aiming to notch up his first strike against Man United. The ex-Atletico Madrid star has already shrugged one monkey off his back this week by netting against his old crosstown rivals, and he'll be the man the Reds look to as they attempt to re-enter the title race on Saturday.
Funnily enough, the Red Devils began 2009 as outsiders on the domestic scene. Their sojourn in Japan for the Club World Cup - and the stuttering form of Luiz Felipe Scolari's Blues - allowed the men from Merseyside to gallop clear at the tabletop at the turn of the year.
But a run of 11 straight league wins since Boxing Day has seen United reclaim their perch at the summit of the standings. They will hope to continue that trend when they host the Reds on Saturday lunchtime, and none more so than Scouse striker Wayne Rooney.
"I grew up an Everton fan, my whole family are Everton fans and I grew up hating Liverpool – and that hasn't changed," the former Goodison Park hero said on Thursday.
"I think coming to Old Trafford will be a difficult game for them. They know they need to win, they need the three points. I'm sure they will be up for it and we certainly will be too.
"It will certainly end Liverpool's chances if we win and that's why we're looking forward to it."
United come into the clash in high spirits and surrounded by talk of a 'Quintuple' after their Champions League triumph over Inter, but their upcoming opponents should take even more confidence from their midweek exploits.
You wouldn't have known Liverpool were struggling for form if you watched their demolition of Real Madrid on Tuesday evening.
Having grabbed a 1-0 win in the first leg at the Santiago Bernabeu thanks to an air-tight defensive display, the Mersey giants then proceeded to put four unanswered goals past a helpless Iker Casillas in the return fixture, thus booking their sport in the quarter-finals.
However, as is so often the case with Rafael Benitez's side, their European efforts are in no way reflective of their domestic situation. For example, the impressive victory in Spain two weeks ago was followed up immediately by a disastrous 2-0 defeat at Middlesbrough. Many would would tipping a similarly sluggish showing at Old Trafford this weekend.
Liverpool haven't fared especially well in their arch-rivals' den over the past few years; in fact, the last time they returned with three points in league play was in 2004, when Danny Murphy was the hero. However, they are yet to lose against a Big Four opponent this term, and they will hope to replicate their 2-1 victory over Sir Alex Ferguson's champions at Anfield earlier in the campaign.
The Reds, who have won just three league games since their 5-1 mauling of Newcastle United at the end of December, are well aware that defeat against United would end their title chase once and for all. And Martin Skrtel has assured the Kopites that they will be going all-out for the win.
The Slovakian centre-half, who starred against Los Blancos, said recently, "Any result other than a win would mean a definite end to our title hopes.
"Despite the point difference, we are going into the match with the goal of winning. We will see if we can do it but, one thing is for sure, we are in a good mood after beating Real."
And as United would draw level with Liverpool on 18 English championships should they win this season, there is no lack of motivation for Benitez's boys.
FORM GUIDE
Manchester United
Mar 11 Man United 2-0 Inter (Champions League)
Mar 07 Fulham 0-4 Man United (FA Cup)
Mar 04 Newcastle 1-2 Man United (Premier League)
Mar 01 Man United *0-0 Tottenham (Carling Cup)
Feb 24 Inter 0-0 Man United (Champions League)
Liverpool
Mar 10 Liverpool 4-0 Real Madrid (Champions League)
Mar 03 Liverpool 2-0 Sunderland (Premier League)
Feb 28 Middlesbrough 2-0 Liverpool (Premier League)
Feb 25 Real Madrid 0-1 Liverpool (Champions League)
Feb 22 Liverpool 1-1 Manchester City (Premier League)
TEAM NEWS
Manchester United
Ferguson's defence remains light on personnel, with Gary Neville, Wes Brown and Rafael da Silva all sidelined, but Rio Ferdinand is expected to start after coming through Wednesday's win over the Nerazzurri unscathed. The very capable Jonny Evans will be on stand-by.
Rooney is likely to partner Dimitar Berbatov in attack, although Carlos Tevez - who scored at Anfield in October - may well feature in some capacity.
Possible XI: Van der Sar - O'Shea, Ferdinand, Vidic, Evra - Ronaldo, Carrick, Scholes, Giggs - Berbatov, Rooney
Liverpool
Albert Riera should return to the starting lineup after missing the midweek mauling of Madrid through suspension. Ryan Babel will most probably make way, despite a bright showing against the Merengues.
Danish defender Daniel Agger is still hampered by a back problem, but Yossi Benayoun - who hasn't played since scoring at the Bernabeu last month - is a chance to make the squad as he recovers from a hamstring problem.
Possible XI: Reina - Arbeloa, Carragher, Skrtel, Aurelio - Mascherano, Alonso - Kuyt, Gerrard, Riera - Torres
PLAYER TO WATCH
Manchester United
After his controversial comments during the week, all eyes will be on Wayne Rooney as he attempts to kill off Liverpool's title hopes. The 23-year-old is perhaps not in the finest form of his career, but everyone knows what the former Evertonian is capable of.
Liverpool
At the other end of the park, Fernando Torres will be aiming to notch up his first strike against Man United. The ex-Atletico Madrid star has already shrugged one monkey off his back this week by netting against his old crosstown rivals, and he'll be the man the Reds look to as they attempt to re-enter the title race on Saturday.