Liverpool face a daunting trip to Manchester City in the standout tie of the FA Cup quarterfinals this weekend as Mohamed Salah seeks to end nine spectacular seasons at Anfield on a high.
Arsenal and Chelsea will expect to reach the semifinals at Wembley against lower-tier opposition, while West Ham and Leeds put their battle for Premier League survival on hold in a bid to reach the last four.
We examine what to look out for in the four ties:
MANCHESTER CITY V LIVERPOOL, SATURDAY 13:45 (ALL TIMES CAT)
City produced perhaps their best performance of the season to dominate Arsenal and win the League Cup final 2-0 before the international break.
They remain in the running to match their feat as the only English side to ever win the domestic treble of League Cup, FA Cup and Premier League in 2018-19.
Liverpool face a defining 10 days for their season and possibly Arne Slot's future at Anfield.
Languishing fifth in the Premier League, the FA Cup and Champions League are the Reds' only remaining hope of glory.
After visiting the Etihad, Slot's men face European champions Paris Saint-Germain in the Champions League quarterfinals over two legs on 8 and 14 April.
Despite leading Liverpool to a record-equalling 20th English top-flight title less than a year ago, Slot is under huge pressure to end a difficult second season on a high if he is to remain in the job.
The rest of Liverpool's season will also be marked by a long farewell to Salah.
The Egyptian announced over the international break that he will leave at the end of the campaign, having netted 255 goals so far for the club.
"Hopefully, he can make his legacy even more special in the upcoming weeks and months, where we still play for something special, but he will always leave this club as a legend," said Slot.
CHELSEA V PORT VALE, SATURDAY (18:15)
Chelsea can ill afford to add a massive cup upset to a maelstrom of discontent on and off the pitch at Stamford Bridge.
Four consecutive defeats have plunged manager Liam Rosenior's future into doubt less than three months into his reign.
Enzo Fernandez and Marc Cucurella have spoken out publicly in recent weeks, criticising the decision to sack Enzo Maresca in January.
Chelsea then announced a Premier League record pre-tax loss of £262.4 million ($349.3 million) for the year to 30 June on Wednesday, sparking speculation over who the Blues may have to sell this summer.
A Port Vale side rooted to the bottom of League One and headed for the fourth tier should still pose little problems for the Premier League giants.
But Vale have won as many games in the FA and League Cup this season (seven) as they have in 38 league games.
SOUTHAMPTON V ARSENAL, SATURDAY (21:00)
Mikel Arteta's team selection will be scrutinised at St. Mary's after most of his key players pulled out of international duty with injuries.
Declan Rice, Bukayo Saka, William Saliba and Gabriel Magalhaes were among the 10 Gunners to withdraw from action with their nations.
Arteta is seeking a reaction after Arsenal's six-year wait for a trophy was prolonged by City at Wembley.
But they remain in pole position for a first Premier League title in 22 years and also have a favourable Champions League quarterfinal draw against Sporting Lisbon.
WEST HAM V LEEDS, SUNDAY (17:30)
The priority for both sides may be Premier League survival, but the draw has handed them a rare chance to make the last four.
Leeds have not reached the FA Cup semifinals since 1987, while West Ham last made it that far 20 years ago.
West Ham sit in the Premier League relegation zone, four points adrift of Leeds, but have used the positive momentum of a cup run to turn their season around.
Since ending a 10-match winless run against QPR in the third round, Nuno Espirito Santo's side have lost just three of 13 games.