Liverpool's visit of fierce rivals Manchester United takes centre stage as the FA Cup resumes with a jam-packed weekend of fixtures.
The glamour tie of the fourth round will take place on Saturday lunchtime with Anfield as the stage, with the Reds having already booked one Wembley visit after advancing to the Carling Cup final with a win over Manchester City in midweek.
The clubs have joined forces in calling for both sets of fans to act responsibly, with the clash marking the first time the teams have met since Luis Suarez was banned for eight matches for racially abusing Patrice Evra in October, but tensions are expected to run high in a fiercely-contested affair.
Two Friday evening games are scheduled ahead of that showdown, one of which will see Tottenham make the short trip to Championship opponents Watford, with Spurs boss Harry Redknapp set to return to the dugout.
Redknapp has not been able to take a training session this week as he has been on trial at Southwark Crown Court contesting two counts of cheating the public revenue, but will be present at Vicarage Road as the Hornets look to cause upset against the Premier League high-fliers.
In Friday's other encounter, two top-flight opponents go head-to-head when Everton host Fulham at Goodison Park, with in-form Cottagers striker Clint Dempsey seeking his third hat-trick this month.
West London rivals QPR and Chelsea meet at midday on Saturday for the first time since the eruption of the John Terry and Anton Ferdinand race row, with new Rangers boss Mark Hughes looking to overthrow the heavyweights after leading his side to their first FA Cup win since 2001 in the third-round replay against MK Dons last time out.
Arsenal will also go up against top-flight opposition but will have to wait until Sunday to do so when they entertain Aston Villa at Emirates Stadium, with the Gunners looking to atone for their deflating defeat to Manchester United in the league last weekend.
Both West Brom and Norwich will be keen to keep their only hope of silverware this season alive when they collide at the Hawthorns, with the promoted Canaries likely to be feeling confident after climbing into the top half of the league table thanks to a four-game unbeaten run.
In the final all-Premier League encounter of the round, four-time cup winners Bolton host top-flight newcomers Swansea seeking revenge after the Welsh side ended a run of nine winless games against the struggling Trotters in October with a 3-1 triumph at the Liberty Stadium.
Last year's runners-up Stoke are one of four top-flight sides who will face Championship opposition in this round as they prepare to visit local rivals Derby County, who have won five of their last six games in all competitions and are just two points adrift of the play-off places.
Newcastle, this season's surprise package of the Premier League, also go up against competition from the second-tier when they travel to Brighton, who have enjoyed a recent resurgence to revive their hopes of Championship promotion this season and will hope to continue that run against Alan Pardew's high-fliers.
In Sunday's other encounter, mid-table Sunderland entertain Championship outfit Middlesbrough looking to maintain their turnaround under new manager Martin O'Neill, having lost just one in their last seven in all competitions.
Crawley Town will be eager to repeat their feat of reaching the fifth round when they travel to Hull City, having come close to forcing a replay against eventual semi-finalists Manchester United last season.
Crawley's League Two rivals Swindon are the lowest ranked side left in the tournament and face a daunting task against Championship promotion hopefuls Leicester but will be boosted by their upset of Premier League strugglers Wigan last time out.
Two sides from opposite ends of the Championship will collide when struggling Millwall host title hopefuls Southampton at The Den, with the Lions looking to capitalise on their visitors' recent slide of three defeats in four league games.
Sheffield United have only come up against lower league opposition so far and face their first real test when they host Championship side Birmingham City at Bramall Lane, with the promotion contenders keen to get back to winning ways after defeat to Charlton in League One last time out.
The Blades' fierce city rivals Sheffield Wednesday are another third-tier club still in contention and head to Bloomfield Road hoping to upset a Blackpool side unbeaten in four in all competitions.
In the weekend's final encounter, two League One opponents go head-to-head as promotion hopefuls Stevenage entertain Notts County, whose cup triumph over Doncaster in the third round marked the only win of their last nine games.