Liverpool will host Manchester United at Anfield on Sunday with both clubs set to pay their respects to the 96 people who died in the Hillsborough disaster.
The revelations set out in the Hillsborough Independent Panel's Report two weeks ago sent shockwaves that resonated far beyond the footballing world, and Liverpool skipper Steven Gerrard and his United counterpart, Nemanja Vidic, will release 96 balloons into the air to commemorate those who lost their lives on April 15 1989.
Several individuals from both sides have called for a respectful atmosphere at Anfield, with vile chants about the Hillsborough and Munich disasters often overshadowing the sporting reasons for the clubs to be great rivals.
The pre-match handshakes will be keenly watched by all, with an opportunity given to bookend the controversy surrounding Patrice Evra and Luis Suarez, who was charged with racially abusing the Frenchman following the corresponding fixture last season.
The striker then snubbed Evra in the pre-match pleasantries at Old Trafford later in the season, but has a chance to put things right on Sunday.
Elsewhere, another huge clash in the North West sees Arsenal travel to the Etihad to face champions Manchester City.
The Gunners have made a fine start to life without Robin van Persie, remaining unbeaten and only conceding once in the league so far, with a 6-1 drubbing of Southampton last time out proving they have not lost their attacking potency.
Roberto Mancini's side have stuttered so far, but their home dominance remains unwavering, having won both ties at the Etihad this season. The Blues have not lost on their own patch for 31 games, having won 29 of those encounters.
Chris Hughton takes his Norwich side to Sports Direct Arena, his first return to Newcastle United since being sacked as manager in 2010.
The man who replaced him, Alan Pardew, has enjoyed incredible success in the intervening period and will be looking for a second home win of the season, while the Canaries still search for their first victory of the campaign.
Finally, a London derby rounds of a scintillating set of fixtures, with QPR travelling to White Hart Lane to take on Tottenham.
Spurs have drawn all three of their home games under Andre Villas-Boas but will go in as heavy favourites, with the Hoops having taken a single point from all away games since Mark Hughes took over as manager in January.