In the years gone by this fixture's result would go a long way toward which team would march away with a Premier League crown on their heads.
Some things never change, but after the systematic collapse of Manchester United over the past few months, the tie takes on a new relevance.
As Arsenal overachieve, and station themselves back at the summit of England's top division, the reigning champions have transformed into a mid-table side, to the horror of their loyal support.
United's form has been shot to ribbons as they now lie in 11th position in the Premier League Form table.
Arsenal themselves could be on the verge of a crisis after being decimated by Liverpool last Saturday 5-1.
A victory against United is the tonic that Arsene Wenger's men need but should they fail and allow United to recapture some much needed temporary glory, they could find themselves spiralling quickly from the title picture.
Here are the top stars to watch in this intriguing match:
When Arsenal made Mesut Ozil from Real Madrid their record signing, they knew just exactly what they were getting.
Ozil's stock exploded during his time in La Liga, earning his reputation as an assist machine alongside the mercurial Cristiano Ronaldo.
It was this quality that Wenger wanted to bring to the Emirates—a player of true world-class standing to compliment the Jack Wilsheres and Aaron Ramseys.
With Arsenal finally mounting a serious championship challenge, Ozil's figures of eight assists and four goals in 20 matches look credible, per WhoScored.
However, under deeper scrutiny Ozil's contribution does not stand up, only providing two assist in the last 10 games, and not scoring a single goal.
This has led to rumblings that the German might need a rest after having to adjust to the fast pace of the Premier League and having to forgo a mid-season break like his compatriots on the continent exercise.
But the truth is Ozil has not helped his team when they have needed it most.
Against Liverpool the player was a passenger, not able to positively influence the game at all. This led to a rampant Luis Suarez and company having the space to destroy Arsenal, and the game was effectively over in 20 first-half minutes.
If he starts, the game against United is the perfect opportunity to get his season back on track. By all means he has not been poor this season, but with his price tag comes an added weight of expectation, and the little wizard needs to deliver.
United have huge issues in midfield and Ozil can exploit this weakness. However, if he fails, and the poor central core of the Red Devils restricts him, he will find it a struggle to drive Arsenal on to the title in the last quarter of the season.
Robin van Persie
There will always be a stench in the air for Arsenal fans when their former captain arrives in town, ready to bury the ball in their net.
Robin van Persie has gone from always fit and always scoring, to hardly being available and always injured in the space of just a few months.
His scoring record has been maintained though: In his 14 Premier League matches this season he has netted 10 times, per Squawka.
But there are rumblings of a shock exit from United, as tweeted by John Cross of The Mirror, with Wenger not ruling out the possibility of a move for his former player:
Rob Shepherd of The Daily Mail also suggested that van Persie could return to his former club after becoming disillusioned after the retirement of Sir Alex Ferguson and the departure of Rene Meulensteen.
However, the player himself has given David Moyes and United his own personal vote of confidence in a recent interview:
Now RvP is fit it is time for him to improve his form to match that of his goal-scoring record. The Dutchman has always been more than just a striker and has a fluid approach to forward play.
The game is so important to both teams for different reasons but on this occasion I can only seeing one team prevailing.
Despite their humbling last weekend, Arsenal's form and quality have been assured all season and I fully expect them to see off a United side that lack quality and confidence.
The later that the match journeys towards the final whistle with the scores level, the greater the opportunity for United to strike. It will not be long before van Persie, Rooney and Mata combine to deadly effect, but I doubt it will happen in this game.
Will Robin van Persie score against Arsenal on Wednesday night?
Wenger knows that if his team is to stay in touch with Manchester City and Chelsea it is these kind of big matches that his team will need to win.
I think United will struggle to score against a mean Arsenal defence, and with Ozil pulling the strings advanced in midfield, the Gunners should make the job look comfortable.
Predicted Score: 2-0