Manchester United continue their quest for a fourth successive Premier League title when they go head-to-head with Fulham at Old Trafford while Manchester City visit Sunderland on Sunday.
Sir Alex Ferguson's men will be sky-high following their Champions League success over AC Milan but Fulham, under their shrewd boss Roy Hodgson, are made of stern stuff these days and have enjoyed a positive run in Europe as well this term.
They are in the middle of a two-legged Europa League last-16 clash with Juventus and sit comfortably in tenth place in the league table.
Bobby Zamora is in fine goalscoring touch for the Cottagers of late and will be keen to continue his exploits in the north-west.
United have lost just one of their previous 11 fixtures on the domestic front - a 3-1 reversal at Everton - and, as ever, all eyes will be on dynamic forward Wayne Rooney.
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The England star has netted 23 league goals so far this term and will be looking to extend his lead in the scoring charts over Chelsea's Didier Drogba.
A win for United would pile further pressure on fellow title-contenders Chelsea and Arsenal.
Fulham's form is admirable and they have gone five games unbeaten in the league but the Red Devils will be a wounded beast after their meeting at Craven Cottage in December when they limped to a 3-0 defeat.
They must do it without Anderson (knee) and Michael Owen (hamstring) though, who will be missing for the rest of the season. John O'Shea (thigh) is also a long-term absentee.
Andrew Johnson (knee) will be missing for the visitors and he is unlikely to return before the season draws to a close.
Clint Dempsey, John Paintsil and Kagisho Dikgacoi (all knee) are nearing fitness but Sunday's clash may come too soon for them.
Meanwhile, Sunderland will be looking to build on their midweek win against Bolton Wanderers when they welcome Manchester City to the Stadium of Light.
Steve Bruce's struggling side grabbed a much-needed 4-0 win against the Trotters, with Darren Bent notching a hat-trick, and the timing couldn't have been better.
The Black Cats had laboured to 14 games without a win before Tuesday night's triumph which lifted their mood ahead of the tricky test against Roberto Mancini's outfit.
Sunderland now sit six points ahead of Hull City in the third and final relegation place with just ten games of the Premier League season remaining.
City secured a fantastic 4-2 win at Chelsea last time out when Craig Bellamy and Carlos Tevez both bagged braces in a heated contest at Stamford Bridge.
They are now the online betting favourites to secure fourth spot in the Premier League and a place in next season's Champions League.
However, before the Stamford Bridge success, they had collected just four points out of a possible 12 on offer.
They currently occupy fifth place in the table, level on points with Tottenham Hotspur, who sit above them on goal difference.