In a gripping title race, Arsenal and Manchester City will hope for a Liverpool stumble, while the top four battle and relegation survival fight are also heating up.
AFP Sport looks at three talking points ahead of this weekend's action:
No 'revenge' mission for Liverpool
With memories of their painful FA Cup quarter-final defeat at Manchester United still fresh for Alexis Mac Allister and his Liverpool team-mates, it would have been no surprise if the Argentine midfielder had branded their return to Old Trafford as a revenge mission.
Jurgen Klopp's side twice blew the lead in a 4-3 defeat that was clinched by Amad Diallo in the final seconds of extra-time.
The end of Liverpool's quadruple bid stung the Merseysiders but they can make amends by defeating Erik ten Hag's men as they bid to move level with United's record 20 top-flight titles.
Mac Allister, whose thunderous strike put Liverpool on course for their 3-1 win over Sheffield United on Thursday, insisted avenging their FA Cup loss was not the primary motivation with so much already at stake.
"I don't know if it's revenge but for sure it will be an important game for us because if we want to win something we have to win every game and that's the aim," said Mac Allister, whose team are two points clear of second-placed Arsenal with eight games left.
Arsenal head to Brighton aiming to keep the pressure on Liverpool, while third-placed City - three points behind the leaders - travel to Crystal Palace.
Top-four race heats up
Tottenham are not the "finished article" according to boss Ange Postecoglou as his top four hopefuls face a vital weekend in the race to qualify for the Champions League.
Postecoglou's side were held to a frustrating 1-1 draw at West Ham on Tuesday but Aston Villa's 4-1 defeat at Manchester City 24 hours later kept the north Londoners firmly in contention for a top-four berth.
Fifth-placed Tottenham are two points behind fourth-placed Villa with a game in hand.
Struggling Nottingham Forest visit the Tottenham Hotspur Stadium on Saturday, while Villa host Brentford.
Both sides will be expected to win and a shock slip-up could be a decisive moment, with Postecoglou conceding his team are still a work in progress.
"I would love to have a joystick and put them where I want them but it doesn't work like that. We are not the finished article and we know that," he said.
Villa are aiming to play in the Champions League for the first time since 1983 and boss Unai Emery said his players relish the pressure.
"We will play a lot of matches in the next weeks, starting on Saturday. It's clear we are motivated and excited to try to be competitive," he said.
'Only way is up' in survival battle
Nottingham Forest midfielder Morgan Gibbs-White is confident his side will not crack as the tension mounts in the struggle for survival.
Gibbs-White scored as fourth-bottom Forest defeated Fulham 3-1 on Tuesday to improve their hopes of beating the drop with a first win in seven games in all competitions.
"Credit to the whole team. It looks like the only way is up from here, hopefully," Gibbs-White said.
Forest have been deducted four points for breaching the Premier League's profitability and sustainability rules, while Everton were hit with a six-point punishment - reduced from 10 on appeal - for similar financial offences.
Everton face boss Sean Dyche's former club Burnley in a crucial clash at Goodison Park on Saturday when the Toffees will bid to snap a club record 13-game winless Premier League run.
Dyche's side are seven points above second-bottom Burnley as they chase their first league win since beating the Clarets in December.
Third-bottom Luton host Bournemouth looking to close the three-point gap on Forest.
