Sir Alex Ferguson's Premier League giants come to town on Saturday, with the Royals looking to record their first ever league win over the Red Devils.
But Brian McDermott's men will be out to change the course of history come 5.30pm on Saturday - as Reading strive to beat Manchester United for the first time in 85 years. Monday 17th January 1927. The last time - and the only time the Royals have triumphed over the Mancunians in all competitions.
Before Reading first arrived in the Premier League in 2006, they had faced Manchester United ten times in the FA Cup - but only once came out on top. In 1912, the Biscuitmen forced United to a replay after a 1-1 draw at Elm Park - but were beaten 3-0 in reply at a very infant Old Trafford ground.
But 1927 was the be the Royals' year. After denying United twice at Old Trafford, Reading claimed victory in the second replay with a 2-1 win at Villa Park. Frank Richardson, who netted four times over the three encounters, inspired the Royals to victory and launched a marvelous FA Cup run which only lost its legs at the semi-final hurdle.
The Royals gave United another scare in 1955 - forcing Sir Matt Busby's babes of Roger Bryne, Bill Foulkes and Duncan Edwards to a replay - but were thwarted at the Theatre of Dreams. Though the Royals lost 3-2 to a United side that included George Best, Dennis Law, and Bobby Charlton in the short-lived pre-season Watney Cup in 1970, Reading had to wait another 41 years until our next FA Cup encounter with Man Utd - and in 1996, Eric Cantona, Paul Parker and a young Ryan Giggs reigned supreme.
Fast-forward ten years to September 2006. Perhaps the closest the Royals have come to notching a league win over Man United came when Kevin Doyle thumped Steve Coppell's army to the verge of creating history - but a late Cristiano Ronaldo strike denied Reading.
No Ronaldo this time - but the likes of Wayne Rooney and Paul Scholes, who played that day, will link up with the impeccably exceptional talent of Robin van Persie.
It doesn't get any easier. But one things for sure, the Royals walk out to an incredible atmosphere, looking to tear out the history books and right their very own chapter on what will hopefully be a truly memorable, historic night in Berkshire.