Liverpool travels to Manchester City with a seven-point advantage over the Premier League champion at the summit.
The outcome at the Etihad Stadium on Thursday is likely to be viewed as a pivotal moment, whichever way this season's title race is settled.
But the victor in such battles does not always win the overall war.
Here, we look at some memorable Premier League tussles between title contenders and – crucially – what happened next.
Newcastle 0 Manchester United 1 (March 1996)
Until Sergio Aguero authored the most dramatic finish in Premier League history, Manchester United's pursuit of Kevin Keegan's Newcastle United was the division's most famous title race. The Magpies had been 12 points clear at the top in January but the reigning champion gradually trimmed that advantage and an incredible goalkeeping performance by Peter Schmeichel, coupled with Eric Cantona's winner, saw it cut it to a point with victory at St. James' Park.
As their fight reached its conclusion, Alex Ferguson successfully got under Keegan's skin by suggesting teams like Nottingham Forest and Leeds United would not try as hard against Newcastle as they would against United. That prompted Keegan's infamous "I would love it" rant, making it clear the Newcastle boss had lost both control and the title race as United went on to win the league by four points.
Manchester United 0 Arsenal 1 (March 1998)
Having lost out to Blackburn Rovers in 1995, United's dominance of the Premier League was interrupted again by Arsene Wenger and Arsenal, who looked unlikely title winners until they blew the race wide open courtesy of Marc Overmars.
The Dutchman gave Arsenal its just reward for an excellent performance when he latched on to Nicolas Anelka's flick-on. Victory moved the Gunners within six points of United at the top but with three games in hand, and they never looked back, clinching the title with two matches to spare in a 4-0 win over Everton.
Manchester United 0 Arsenal 0 (September 2003)
United was again dethroned by Arsenal in 2003-04, but in much more emphatic fashion than anyone could have expected. Wenger's side appeared poised for a first defeat of the season at Old Trafford after Patrick Vieira was sent off and United was awarded a 90th-minute penalty. However, Ruud van Nistelrooy clattered against the crossbar and was subsequently surrounded by Arsenal players celebrating his failure, with six of them charged by the FA in the aftermath. Arsenal would rarely come closer to defeat as Wenger masterminded one of the best seasons in Premier League history, the Gunners going the entire campaign unbeaten and becoming "The Invincibles". Their streak extended to 49 matches before being ended in a 2-0 defeat at Old Trafford.
Manchester United 1 Liverpool 4 (March 2009)
Liverpool's efforts to win the title in the Premier League era have been tales of frustration and near-misses, and that was the case in 2009 despite a memorable win at Old Trafford. A Fernando Torres strike and a Steven Gerrard penalty turned the game on its head after Cristiano Ronaldo had given United the lead. Fabio Aurelio and Andrea Dossena scored stylishly to trim the deficit to four points. That is the best-case scenario for Guardiola on Thursday, who might note Rafael Benitez's Liverpool was unable to rein in United.
Manchester United 1 Manchester City 6 (October 2011)
The noisy neighbour made its biggest racket of all as Roberto Mancini's side delivered one of the great Manchester derby performances, humiliating United on its own patch to go five points clear at the top.
The image of Mario Balotelli lifting his shirt to ask "Why always me?" is the abiding one from that game and it was the Italian who laid on the key pass for Aguero as he fired home City's incredible stoppage-time winner to clinch the title on the last day with a 3-2 comeback victory over QPR. Goal difference was all that separated the Manchester sides, meaning the Old Trafford rout seven months earlier remained key.
Manchester City 2 Manchester United 3 (December 2012)
A battle of the unbeatens went in the favour of the Red Devils as they earned a crucial victory en route to the title in Ferguson's final season as a manager. Robin van Persie claimed the points with a deflected free-kick in injury time after Wayne Rooney's brace had been cancelled out by Yaya Toure and Pablo Zabaleta, sending United six points clear at the summit. It went on to take the crown back from City, winning by 11 points.
Liverpool 3 Manchester City 2 (April 2014)
A thrilling victory on the 25th anniversary of the Hillsborough disaster looked like being decisive in ending Liverpool's long wait for Premier League glory. Philippe Coutinho's winner sent Liverpool seven points clear of City, though Manuel Pellegrini's men had two games in hand. Sensing the one trophy that eluded him was within his grasp, Steven Gerrard gave a passionate on-pitch speech to his players informing them that "this does not slip now". Contrary to his instructions, it did. An infamous stumble from Gerrard let Demba Ba in for a key goal as Liverpool lost 2-0 to Chelsea and Luis Suarez was left in tears after a dramatic 3-3 draw at Crystal Palace. City, by contrast, was the picture of consistency and clinched the title with a 2-0 final-day win over West Ham.
Arsenal 2 Leicester City 1 (February 2016)
Leicester's scarcely believable title triumph may never have happened had Arsenal capitalised on the double it did over the Foxes. Danny Welbeck glanced home a winner deep into added time that pulled the Gunners to within two points of Claudio Ranieri's surprise package.
However, Arsenal dropped points in seven of its final 12 matches, blowing its best chance to regain the title under Wenger's stewardship as Leicester completed the impossible and finished 10 points clear.