Manchester United host Chelsea this Sunday for one of the most crucial Premier League matches of the season so far.
A win for United would take them six points clear of the reigning champions who trail the Old Trafford club at the top of the table.
The Red Devils' goalkeeper Edwin van der Sar said: 'It doesn't get much bigger than this.
'When we played them at home last season we were 10 points behind, so it goes without saying we are in a better position.'
The battle for supremacy between the two sides has accelerated, with Chelsea chief executive Peter Kenyon declaring that Chelsea will be the biggest club in the world by 2014; a suggestion later ridiculed by Sir Alex Ferguson.
On Saturday, Arsenal travel to the Reebok Stadium to take on Bolton Wanderers, but do so without captain and talisman Thierry Henry, who has been ruled out with a neck injury.
Bolton lie just one point behind the misfiring Gunners and a win on Saturday could jump them up to third position in the table.
Arsenal manager Arsene Wenger has attacked Bolton's up-and-at-them tactics in the past, but Bolton manager Sam Allardyce chooses to take the criticism as a compliment.
He said: 'It is wonderful to hear Arsene Wenger slaughtering our tactics.
'It is a great honour for me to hear any manager slagging Bolton off, particularly when it is one of the big boys.
Elsewhere, West Ham face Sheffield United at home for their first game under new Icelandic owner Eggert Magnusson.
Manager Alan Pardew told the BBC: 'The message has been loud and clear about building a positive future for the club.
'Now we need to match that in terms of moving up the league table.'
It remains to be seen whether some much needed stability will return to the club now the drawn out takeover process nears completion.
Both West Ham and the Blades have struggled for form this season with both resting just above the relegation zone.
Saturday's tie between Liverpool and Manchester City sees the Merseyside club try and carry their Champions League form into the Premiership.
Liverpool top Champions League Group C after a 2-0 home victory over PSV Eindhoven on Wednesday.
Reds striker Peter Crouch said: 'In the Champions League our form has been good so hopefully we can take that into the Premiership.
'Our home form is good and we want to keep that going.'
Rafael Benitez expects to have Craig Bellamy in his squad for the clash with City at Anfield, despite the Wales striker's continued involved in a court case in Cardiff.
Liverpool are without Xabi Alonso and Mark Gonzalez with hamstring problems, while Jermaine Pennant is doubtful with a similar strain.
Manchester City are yet to win away from home this season, but manager Stuart Pearce believes that a European place is still a possibility.
He said: 'We have done well in the last couple of matches and beating Liverpool at Anfield would give us an immense lift.
'Everybody outside the top three or four will be looking at a European place and we are no different. We are only seven points behind the third-placed team.
'We know if we beat Liverpool we go above them and I don't think it is unreasonable that we will.'
Saturday's lunchtime fixture sees Les Reed's first match in charge of Charlton at The Valley, as they play host to Everton.
Striker Jimmy Floyd Hasselbaink is missing for the Addicks following a thigh injury. Midfielder Amady Faye returns from suspension, while defender Souleymane Diawara remains a doubt with a suspect hamstring.
Everton are suffering from a depleted squad with boss David Moyes complaining of a lack of personnel.
He said: 'We are short of numbers at the moment. We were short before we started the season and we don't have that many injuries.'
Fulham and Reading meet at Craven Cottage on Saturday and victory in the mid-table clash propelling the Cottagers ahead of the Royals'.
'I'm not looking at who's above us,' insists Fulham midfielder Michael Brown. 'We just need to get a win quickly so we can get back into that top half.'
'We've been there for most of the season and we need to get the win.'
Portsmouth make the long journey to Newcastle on Sunday for the lunchtime fixture.
The Magpies are on a high after Thursday night's 2-1 UEFA Cup victory over Celta Vigo, which saw them qualify for the knockout stages.
The last time the two sides met at St James' Park Newcastle romped to a 3-0 victory in the Carling Cup.
Pompey have lost their last three away Premiership ties, but are still riding high in third place in the league.
They will be looking to turn their away form around to keep them in contention for a top three place at the turn of the year.
Newcastle are missing Damian Duff, but Scott Parker, Oba Martins and Kieron Dyer are all set to return.
Tottenham and Wigan meet at White Hart Lane on Sunday in what is set to be a classic mid-table battle.
The Latics have taken 13 points from the last 15 after enduring a slow start to the season and the Wigan players will be eager to impress after chairman Dave Whelan announced he will make funds available to bring in several signings in January.
Emile Heskey could return for the clash after missing the last three weeks with a calf injury.
Spurs pulled off an impressive 1-0 Uefa Cup victory away to Bayer Leverkusen on Thursday night which will have served to boost their confidence after an uneven spell in the league.
Jermaine Jenas is nursing a calf injury and is a doubt, but Aaron Lennon, Teemu Tainio should make their return as should Pascal Chimbonda who can expect a hostile reception from the fans of former club.
With Aston Villa unbeaten at home, and Middlesbrough without an away win, the form book certainly favours Martin O'Neill's side for their meeting on Saturday.
However, Middlesbrough will have been given a boost after manager Gareth Southgate was granted dispensation to continue managing the club despite not having the necessary coaching badges.
The continuity of management should help them find the consistency on the pitch that has eluded them of late.
Southgate said: 'We know you have to try to string a run of results together to move yourself up the table.
Villa are likely to be without Chris Sutton who picked up a calf knock in training this week, but Stilian Petrov and Aaron Hughes are set to return after missing last week's draw against Wigan.