A place in the quarter-finals awaits the winners of seven intriguing ties, spread over two days, as five Championship clubs bid to claim a top flight scalp.
Given the tumultuous events that have unfolded at Stamford Bridge over the past week, all eyes will be on Vicarage Road, as Chelsea travel to Watford.
New incumbent Guus Hiddink will be at the game, having already met with his players, but it is coach Ray Wilkins that will be charged with the task of picking the side.
Player powerWilkins, brought back to the club by Luiz Felipe Scolari, must put personal loyalty to one side, as Chelsea look to avoid further embarrassment, against a Watford side currently entrenched in the Championship drop zone.
If some press reports are to be believed Gianfranco Zola could be the next through Chelsea's revolving door of managers, should Hiddink's stint prove as short as initially agreed, but with West Ham on the rise of late he might just favour East over West London for the time being.
A prolonged cup run would certainly placate the Italian's ambitions and a home clash against Middlesbrough should, on paper, enable progression.
Gareth Southgate insists his players are up for the cup, amid a battle to retain their top flight status, but a winless league run that stretches to 13 games hardly bodes well for a trip to Upton Park.
Blackburn are another side who would swap a cup run for league survival but given their steady progress under new boss Sam Allardyce, they'll be quietly confident of seeing off Coventry City at Ewood Park.
Cup traditionRovers have an excellent FA Cup record in recent times, having reached the semi-final stage twice in the past four years, while Coventry have to stretch back to 1997/98 for the last time they made the quarter-finals.
Sheffield United have promotion aspirations this season as they sit handily placed in fifth and while Kevin Blackwell will be determined his players remain focused on the job in hand, a Yorkshire derby against Hull City will surely whet the appetite of a Bramall Lane faithful.
Tigers boss Phil Brown will be relieved his side's struggles in the second half of the campaign appear to be easing, with last weekend's draw at Chelsea signalling the end of Scolari, but nonetheless he'll be well aware a trip to Sheffield is never an easy proposition.
Swansea welcome Fulham to the Liberty Stadium in fine form that has seen them climb the Championship table to the fringes of the play-offs.
Fulham's record away from Craven Cottage has been dire this season and with Swans striker Jason Scotland having already bagged 16 goals this term, an upset must surely be in the offing.
On Sunday, Derby County host Manchester United for the second time this season following on from their Carling Cup semi-final clash in January.
Nigel Clough's side were excellent in the first leg at Pride Park and could have taken more than a one-goal advantage to Old Trafford, where they eventually succumbed to the English and European champions.
Derby daysRiled by defeat against Championship opposition, United have been in exemplary form ever since as an eight-game winning run sees them sitting pretty at the Premier League summit.
The weekend's final game pits together two sides who will have genuine aspirations to win the trophy should they progress, with Everton welcoming Aston Villa to Goodison Park.
David Moyes' side have been hugely impressive of late and would perhaps have been in real contention for a UEFA Champions League place, were it not for Villa's invasion of the 'big four' this season.
Last weekend Villa were too good for Blackburn on their travels and Martin O'Neill will be demanding more of the same from his side on Merseyside.
On Monday, the final outstanding tie of the fourth round will be played as Arsenal welcome Cardiff City to Emirates Stadium in their replay.