It's a fixture that is starting to grow in history as cup finals, penalty shootouts, thrashings, red cards and 'dodgy refereeing' all played a big part in recent years.
As the Premier League giants prepare to lock horns in the first-leg battle at Stamford Bridge, Sportsmail looks back on five classic clashes.
United 1-1 Chelsea - Champions League, May 2008 (United won 6-5 on pens)
Despair: John Terry missed a penalty that would have crowned Chelsea as European champions
With the 2008 final in Moscow still sitting fresh in the memory banks it seems unlikely that these sides will ever play a more important or dramatic game against each other.
Ronaldo set United on their way half way through the first period but Frank Lampard equalised before the interval. There were no goals in the second half but Lampard and Didier Drogba struck the woodwork before the game went into extra-time.
Drogba became only the second player to be sent off in the final of the competition after slapping Nemanja Vidic during the additional period before the game went to penalties.
After Ronaldo had earlier seen his penalty saved by Petr Cech, Blues skipper John Terry dramatically slipped to miss the spot-kick that would have won the cup for Chelsea.
In sudden death Edwin van der Sar saved Nicolas Anelka's effort, handing United their third Champions League success.
Moscow turns Red: Manchester United celebrate winning the 2008 Champions League final
Manchester United 3-3 Chelsea - Premier League, September 2000
Both sides harboured ambitions for the Premier League title before the season began but Chelsea came into this game with just one win in their first six matches.
They looked to have turned the corner when Jimmy Floyd Hasselbaink opened the scoring after seven minutes, only for United to hit three first-half replies through Paul Scholes, Teddy Sheringham and David Beckham as the hosts piled more misery on the Blues.
But just before half-time United keeper Raimond van der Gouw flapped at a Tore Andre Flo header to hand Claudio Ranieri's men a lifeline. In the 65th minute, Graeme le Saux's superb goal line clearance denied Andy Cole and it proved crucial, as four minutes later Flo grabbed an equaliser with his second to earn a point for new boss Claudio Ranieri.
On target: Jimmy Floyd Hasselbaink shoots between Paul Scholes and Roy Keane to open the scoring in 2000
Chelsea 5-0 Manchester United - Premier League, October 1999
No one saw this coming. Chelsea wereon form having won all but two of their opening seven games but Unitedwere the treble winners and on a 29-game unbeaten run. But it look lessthan a minute for Gustavo Poyet to head past a Massimo Taibiin no-man's-land, who would have a miserable afternoon in his last gamefor the club.
ChrisSutton pounced 15 minutes later to score his first (and last) leaguegoal for Chelsea before United's Nicky Butt was sent-off for kickingout at Dennis Wise later on in the half. By then the Blues were alreadyin cruise control and scored a third in the second period when Taibiparried Frank Leboeuf's shot straight to Poyet who grabbed his secondgoal of the match.
Onthe hour, Henning Berg directed a cross into his own goal for thefourth before Jody Morris rocketed a fifth through Taibi's legs withnine minutes left.
Chelsea 3-5 Manchester United - FA Cup, January 1998
If this game was 10 minutes longer we could have been in for one of the all-time great FA Cup games. After going 5-0 up, United not only took their foot off the gas but applied the foot and hand brake as well.
David Beckham scored twice in the first-half including a trademark free-kick before Andy Cole struck twice either side of the interval, taking advantage of Chelsea's non-existent defending to beat Ed de Goey with two one-on-ones. With 16 minutes left Teddy Sheringham made it five before United went into total meltdown.
Graeme le Saux started the Chelsea revival four minutes later when he capitalised on careless Beckham defending to cleverly lob Peter Schmeichel. Sub Gianluca Vialli fired past the Dane's near post in the 83rd minute, before Gary Pallister's candidate for worst back-pass of all time allowed Vialli to double his tally two minutes from time, and at least restore some credibility to the scoreline for Ruud Gullit's side.
Manchester United 4-0 Chelsea - FA Cup, May 1994
No penalties needed this time around as Sir Alex Ferguson secured United's first ever 'double' by trouncing Glenn Hoddle's men in a one-sided cup final at Wembley.
Chelsea held firm for an hour but the final was effectively all over just 10 minutes later. Eddie Newton scythed down Dennis Irwin in the penalty box, with Eric Cantona sending Dmitri Kharine the wrong way from the spot in the 60th minute. Six minutes later he replicated his efforts from 12 yards after Frank Sinclair bundled over Andrei Kanchelskis.
Mark Hughes raced on to a through ball before firing past Kharine with 21 minutes left before Paul Ince's unselfish play late on allowed Brian McClair to tap home and complete the rout.
It was an act of revenge too for United, who suffered their only double league defeat against the west London side earlier in the season.
Terry desperate to end Chelsea's Champions League hoodoo at long lastVidic ready for Torres test as United skipper refuses to write off strikerWayne's World falls apart in 12 months: How Rooney fell from graceEXCLUSIVE: The making of the Lampard legend - the family album
Explore more:People: Paul Scholes, Alex Ferguson, Frank Leboeuf, John Terry, David Beckham, Petr Cech, Mark Hughes, Teddy Sheringham, Brian McClair, Frank Sinclair, Frank Lampard, Glenn Hoddle, Jimmy Floyd Hasselbaink, Edwin Van Der Sar, Gary Pallister, Andy Cole, Nemanja Vidic, Didier Drogba, Paul Ince, Nicky Butt, Nicolas Anelka Places: Moscow, London