The champions of the world, Europe and England ardently believe they can achieve their dream of an unprecedented sweep of five trophies this season.
But to rule the continental roost and retain the UEFA Champions League Manchester United must first bury the man who has a better record against them than most. Jose Mourinho's Inter Milan may have struggled to contain United's attacking instincts in their ultimately goalless round of 16 first leg in the San Siro - but if anyone has the Mancunians' number it is the former Porto and Chelsea boss.
The momentum should be with United, who are top of the English Premiership, have the League Cup and the FIFA Club World Cup title locked in the Old Trafford trophy cabinet, plus an FA Cup semi-final and a home return with Inter to look forward to. As United boss Alex Ferguson well knows, however, jousting with Mourinho can be the stuff of nightmares.
The Scot does not have fond memories of his Portuguese counterpart's first UEFA Champions League visit to Old Trafford which saw Porto edge through at this same first knockout stage in 2004 before going on to win the competition.
Mourinho's ambitions to do the same with Chelsea were twice thwarted by Liverpool - but he has a good record in Manchester with just one loss in five visits for his only defeat at Ferguson's hands in 13 meetings. Even so, that statistic cannot disguise the fact the force is very much with United on the Red Devils' current form.
The holders have not lost in 18 home UEFA Champions League matches at Old Trafford and are undefeated in a record 20 competition outings, while Inter are short of defensive numbers after Romanian defender Cristian Chivu was ruled out with a thigh injury. Centre-backs Marco Materazzi and Nicolas Burdisso are also struggling after missing Saturday's 2-0 defeat of Genoa.
Mourinho cavorted down the touchline when Porto ousted United - but midfield veteran Paul Scholes says tough Scot Ferguson won't copy such Latin exuberance. "At his age? He would probably collapse!" Scholes said. "It would be nice to see but I don't think our manager goes in for that type of thing."
All to play for
As Ferguson plots to bring Mourinho down a peg Arsenal will hope to end the campaign of another Serie A side in Roma. Robin van Persie's first-leg penalty separated the sides in London and having kept a clean sheet Arsene Wenger's men, finalists in 2006, fancy their chances of reaching the quarters.
Barcelona, who denied Wenger in the final three years ago, will expect to polish off French serial domestic champions Lyon in the Nou Camp having secured a 1-1 draw in France courtesy of former Gunner Thierry Henry.
Arsenal and Roma have injury worries ahead of their game at the Stadio Olimpico. The Gunners' Togalese forward Emmanuel Adebayor has been ruled out with hamstring trouble while Roma are sweating on the fitness of their emblematic striker Francesco Totti.
The loss of Adebayor is not so serious for the visitors given that Brazilian-born Croatia striker Eduardo is back in business, as proved by his superb goal in Sunday's FA Cup victory over Burnley, when Theo Walcott made a brief appearance after returning from November shoulder surgery. "I haven't made the team yet but Walcott and Eduardo will certainly be in the squad. The more resources you have the better it is and they are two guys who can score goals," Wenger said.
Roma's problems are not confined to Totti, as a question mark hangs over his usual replacement Mirko Vucinic while midfielders Simone Perrotta are both unavailable. Barcelona will be without defenders Carles Puyol, their skipper, and France international Eric Abidal, a former Lyon player, for their meeting with the French champions.
The French will pin their hopes on star striker Karim Benzema, substituted during Saturday's surprise loss to Lille, recovering from a hip injury. "We'll see how he progresses," said Lyon coach Claude Puel, whose side have never been beyond the quarters.
In Wednesday's other game Porto will be straining to go further than their old coach Mourinho as they host an Atletico Madrid side who they held to a share of the spoils, 2-2, in Spain.