With another meeting against Real Madrid looming next Tuesday, Ferguson knows he must get his team selection right at Old Trafford if United are to stand any chance of progressing to the quarter-finals.
That is bound to mean disappointment for some, as it did in the Bernabeu a fortnight ago.
On that occasion, skipper Nemanja Vidic headed a list of high-profile omissions, with neither Ashley Young nor Nani included either.
After watching Real hammer Barcelona in the Nou Camp last night in the first of back-to-back 'El Clasicos' prior to Jose Mourinho's men heading to Manchester, Ferguson knows how important it is that he makes the correct calls.
Yet, even for those who miss out, the United boss can point to a very real example to prove it does not necessarily mean they can never have an impact with the Red Devils.
"In 1999, I left Paul Scholes out of the quarter-final against Inter Milan yet he was the one who scored the goal that got us through," Ferguson told MUTV.
"I left him out of the semi-final because I couldn't risk him and Roy Keane together as they were both on yellow cards. He accepted it graciously, came on, got booked and missed the final anyway.
"What did he do? He didn't let it affect him. He went on to become one of the greatest players this club has ever had.
"The players sense it could be a big year for them.
"But at this club, in this situation, anything can happen on the run-in. Players can all of a sudden find themselves playing in a final or an important league game because that is the kind of squad I have."
The first guide to Ferguson's thinking will come with his team selection for Saturday's Barclays Premier League encounter with Norwich.
Neither Vidic nor Rio Ferdinand are being trusted to play more than a game a week just now, so selection for either man, or omission for that matter, may be telling.
The same is true of Ryan Giggs, whilst Javier Hernandez, whilst much younger, may view getting picked as a signal he will not be against a side so famous in his native Mexico, particularly if Robin van Persie overcomes his hip complaint as expected.
Yet, tempting as it might seem, Ferguson has warned his players not to treat selection for a more mundane domestic fixture as second best.
"It is very difficult to rotate the squad at the moment," he said.
"They all wanted to play against Real Madrid and there were a lot of disappointed players.
"That was fantastic. It is a measure of their own confidence in themselves.
"But we had a chat. I said 'look, don't think for a minute losing a game for Manchester United is a trivial matter'. It is a serious matter."
And with a run of four successive home games, United can heighten their chances of repeating their epic 1999 Treble, especially as the Old Trafford pitch, which Ferguson said had "collapsed" post-Christmas, has been brought back to life.
"The pitch has improved a tremendous amount," he said.
"By the time we play Norwich I expect it will be back to normal so hopefully we can take advantage."