Chelsea will make the short journey across London to the Emirates Stadium to face an Arsenal side looking to end its 12-year wait for the league title.
While the defending champion has endured a disastrous season culminating in Jose Mourinho's dismissal, the Gunners are level at the top of the standings.
In the most unpredictable of seasons, Leicester, a side that was bottom of the table in April, shares the lead with the Gunners, while Manchester City is a point adrift in third.
The onus is on Arsenal to win the title, with several rivals struggling for form. And with Bayern Munich head coach Pep Guardiola available at the end of the season, manager Arsene Wenger will be hoping his side capitalizes on its chance or face the insurmountable criticism and calls for his departure that will likely ensue.
Here are some of the talking points ahead of Saturday's Premier League matches:
No more Mourinho
Fixtures between Arsenal and Chelsea have been notorious for the regularity with which Mourinho would taunt Wenger.
The Portuguese coach would often remind his counterpart of his trophy drought and branded Wenger a "specialist in failure" back in February, 2014.
It will undoubtedly come as a relief to the Frenchman to see a different man standing alongside him on the touchline on Sunday, given his atrocious record against Mourinho.
Just one win in 15 attempts against the former Blues boss, a narrow 1-0 win in the Community Shield, highlighted the superiority Mourinho had in matches that ultimately mattered.
Indeed, a 2-0 home win at Stamford Bridge, while Mourinho was still in charge, saw the visitors finish the game with nine men after Gabriel and Santi Cazorla were dismissed.
Guus Hiddink, who is back at Chelsea for the second time in his managerial career, has been tasked with salvaging its miserable campaign.
However, so far he has guided the Blues to four draws and one win in his first five league games. The squad is largely void of the confidence that it exuded last season as it won the title at a canter.
Last season's player of the year Eden Hazard has yet to score and misses out through injury, and while striker Diego Costa has struggled for consistency this season, three goals in his last four appearances will be of some concern to the Gunners defence.
Tottenham's title tilt
A win for Tottenham away to Crystal Palace on Saturday could provisionally lift Mauricio Pochettino's side to within two points of the summit.
Spurs responded to losing at home to Leicester with a 4-1 thrashing of relegation-threatened Sunderland before exacting some revenge over the Foxes by beating Claudio Ranieri's side 2-0 in an FA Cup third-round replay on Wednesday.
Another London derby pits the North Londoners against Alan Pardew's side, without a win in five league matches.
Three consecutive defeats has seen Palace slip to eighth in the table, and barring favourable results the Eagles could find itself in the bottom half at the end of play on Sunday.
Aguero closing the gap
Sergio Aguero scored twice for Manchester City at home to Crystal Palace last Saturday as they closed the gap at the top of the table.
Despite the striker having suffered with injuries this term, his double against Palace took him onto 10 goals in just 15 appearances this term.
If City is to claim the title for the third time in five seasons, they will need to ensure a clean bill of health for its first-choice striker, who finished top scorer last year with 26 goals.
West Ham caused an upset in the reverse fixture, winning 2-1 at the Etihad in September. That result saw City miss the chance to move six points clear at the top of the table and another defeat would hand Slaven Bilic's side a memorable double and boost its own chances of a top-six finish and European football next season.
Also Saturday: Norwich vs. Liverpool; Leicester vs. Stoke, Manchester United vs. Southampton, Sunderland vs. Bournemouth, Watford vs. Newcastle and West Bromwich Albion vs. Aston Villa. On Sunday, it's: Everton vs. Swansea.