Title-chasing Arsenal must beat bottom club Southampton this weekend if they are to hold off fast-charging Manchester City ahead of next week's Premier League summit meeting.
Tottenham risk losing touch with Newcastle in the battle for a top-four place unless they avoid defeat at St James' Park, while time is running out for Leicester to lift themselves out of the relegation mire.
SuperSport.com looks at some of the key talking points ahead of the action.
MUST-WIN FOR ARSENAL
Arsenal could have been 11 points clear of Manchester City heading into the clash at the Etihad on April 26 but draws against Liverpool and West Ham have cost them.
The Gunners were 2-0 up in both of those matches, adding to the sense of frustration among fans who are desperate to celebrate a first Premier League title triumph since 2004.
If Arsenal beat relegation-threatened Southampton on Friday they will be seven points ahead of Pep Guardiola's men, who are in FA Cup action this weekend. But the Gunners will have played two games more.
Manager Mikel Arteta says his men are ignoring the noise around the City game to concentrate on Southampton.
"We have to become really boring to everybody and be very repetitive, and just focus on what we have to do this morning, and that's it," he said on Thursday.
"What we are playing for is something incredible," he added. "The club hasn't fought for this position for a long, long time. It's in our hands and we want to do it."
MAGPIES EYE TOP FOUR
Newcastle have the chance to put clear daylight between themselves and Tottenham in the race to finish in the top four.
Eddie Howe's team slumped to a 3-0 defeat against in-form Aston Villa last week, ending a five-game winning run, while Spurs conceded a last-gasp goal to lose 3-2 at home to Bournemouth.
Howe accepted it was his side's worst performance of the season but said it was crucial to "focus on what's ahead rather than what's gone".
If Newcastle beat inconsistent Spurs they will leapfrog third-placed Manchester United and move six points clear of Sunday's visitors, with the added luxury of a game in hand.
Aston Villa, who travel to Brentford, are also in the hunt for a top-four place after an impressive run of seven wins in eight games but remain outsiders to qualify for next season's Champions League.
Liverpool also need to be near flawless to climb into top-four contention but will be confident of victory against struggling Nottingham Forest at Anfield.
LEICESTER STARING INTO ABYSS
Leicester won the FA Cup just two years ago and have twice finished fifth in the Premier League in the past three seasons but are staring into the abyss.
The 2016 Premier League champions, who parted ways with manager Brendan Rodgers earlier this month, have lost eight of their past nine league games to plummet down the table.
Dean Smith will take charge of his first home game against Julen Lopetegui's Wolves, who are well clear of the bottom three after an upturn in form.
Smith, a former Villa manager, has urged his team, second from bottom and two points from safety, to play without fear.
Leicester still boast quality players such as James Maddison and Kelechi Iheanacho, who scored a consolation goal in last week's 3-1 defeat at Manchester City.
"We've looked at the quality we have on the training ground, we haven't brought that onto the pitch over the last eight or nine games," said Smith.
"What I saw against Bournemouth (a 1-0 defeat) was lethargy. We need to be free and play with confidence."
Fixtures (1400 GMT unless stated)
Friday
Arsenal v Southampton (1900)
Saturday
Fulham v Leeds (1130)
Brentford v Aston Villa
Crystal Palace v Everton
Leicester v Wolves
Liverpool v Nottingham Forest
Sunday
Bournemouth v West Ham
Newcastle v Tottenham (both 1300)