The inner-city clash has always been a fiery one since it began in 1894, and Wednesday's game will be no exception, with Liverpool hoping to go top and Rafa Benitez looking to win over the Toffees faithful.
But out of all the memorable moments this rivalry has produced over the years, which have been the craziest? talkSPORT EDGE takes a look at 5 of the most jaw dropping…
JEFFERS VERSUS WESTERVELD
It wouldn't be a derby day without fierce rivalry boiling over into some on-field aggression.
So it's only right to include this unforgettable bust up between Everton's Francis Jeffers and Liverpool's Sander Westerveld in 1999 on this list of crazy Merseyside moments.
The pair clashed just 16 minutes before the end of the tie at Anfield, and the incident left referee Mike Riley no choice but to show both players red cards.
Everton were 1-0 up as Francis Jeffers turned to charge at goal, and was quickly flagged offside before running into the Liverpool goalkeeper, Westerveld.
And the entanglement quickly turned nasty as the Dutchman didn't take kindly to Jeffers and swung at him, leading to a brawl.
There ended up being three red cards in the game - a perfect summary of the feelings between the clubs.
SUAREZ MOCKING MOYES
Another crazy incident in the Merseyside derby that has to be mentioned is THAT celebration from Luis Suarez (sorry Moysey…).
The Everton manager had been slating the Liverpool striker prior to the clash, accusing the Uruguayan of having a bad habit of diving and that if his behaviour was mirrored elsewhere it would 'turn the supporters away from football'.
And it didn't take long into the game at Goodison Park for Suarez to get his revenge on the Scotsman.
The Liverpool man found the net after his powerful shot deflected in at the near post off of Leighton Baines's leg in the 14th minute, and there was only one thing on the striker's mind when it came to celebrating putting his side 1-0 up.
The game ended 2-2 with Suarez scoring Liverpool's second to take them 2-0 to the good, only to be cancelled out by Everton.
But despite the Toffees' come back, it was this celebration that will forever remain the talking point of this game in 2012.
GERRARD SPOILS THE PARTY
Former Everton manager David Moyes bore the brunt of another crazy moment in Merseyside derby history earlier that same year when his side faced their rivals on his tenth anniversary.
The fixture marked a decade since the Scot had taken on the Everton hot seat, and a fairytale in the form of a first derby away win at Anfield was waiting for the Toffees boss.
However, in true dramatic derby style, Liverpool made sure to spoil Moyes's party.
The Reds thrashed their rivals 3-0 thanks to a hat-trick from who other than then-Liverpool captain Steven Gerrard, becoming the first player to do so in a Merseyside derby in the league since Ian Rush in 1982.
Liverpool were rampant following their first goal, and their opponents couldn't get a look in, well and truly ruining the party mood for the Evertonian's boss.
And so went on Moyes's long wait for an away derby win with the Toffees.
JAGIELKA'S ROCKET
The fourth crazy Merseyside derby moment that makes the list is Everton's Phil Jagielka's stunning stoppage time equaliser at Anfield in 2014.
The Toffees were 1-0 down in the 91st minute, but come full time it was the away fans, not the Anfield faithful, who were leaving the ground with a spring in their step.
When all hope looked dead and buried, the unlikely goal scorer picked the ball up 30 yards out before rifling an equaliser into the top corner of the Redmen's net.
The centre-back's goal marked one of the most unexpected and heart stopping goals in the rivalry's history.
Following the game, Jagielka said: "We've given the fans too many of these rubbish away days at Anfield so it's nice they've got something to talk about and something to hang on to."
AD BREAK BLUNDER
Perhaps one of the strangest moments in Liverpool-Everton rivalry history happened away from the football pitch.
The clubs faced each other in the fourth-round of the FA Cup back in 2009, and the match was broadcasted live on ITV.
However the cameras managed to miss the only key bit of action in the game when the channel accidentally cut to an ad break which had been accidentally scheduled, just as Everton's Dan Gosling scored the only goal in the game.
Fans watching from home had endured 118 minutes of goalless action, and although some viewers were able to tune back to see Gosling's effort ripple Liverpool's net, most ended up missing it, leaving them furious.
Gosling's winning goal alone deserves a mention considering it knocked Liverpool out of the FA Cup that year, but the ad break disruption definitely won't be forgotten by the Merseysiders on either side of the rivalry.