When Rangers take on United in their Group C opener on Tuesday, Smith will be trying to get the better of the man he worked for twice as an assistant - at United and the Scotland national team - and knows defending well will be the key.
The odds are stacked against him with United winning both of the teams' other meetings and Rangers failing to to win any of their last 10 Champions League matches.
Having worked under Ferguson at United in 2004, Smith did not need Rangers captain David Weir to describe what it was like to play at Old Trafford.
"Manchester United attack you and the majority of the time you end up losing," Weir, sitting next to Smith, told a news conference when asked about his experiences of going there in his Everton days.
Smith, who will retire at the end of this season, was less pessimistic but clear about what his side would need to do: "There will be few teams, if any, that come here and don't place an emphasis on defending."
Whatever happens on Tuesday, Smith and Ferguson - both boyhood fans of Rangers - seem likely to stay friends.
"If I was selecting people to come to a dinner party I would invite him," said Smith. "He enjoys a laugh... and a glass of wine."
Another familiar face for both Smith and Weir from their times at Everton is striker Wayne Rooney, whom Smith signed as a schoolboy and described on Monday as "an outstanding young player, the best I have seen in my own career".
The striker, whose private life has been under the media spotlight for the last 10 days, was left out of the squad to face his old club on Saturday because Ferguson wanted to avoid him facing abuse from fans.
He will return to the side on Tuesday and Weir said there was no point in Rangers fans trying to wind him up.
"I am more interested in Wayne Rooney as a footballer and I don't think there is any need to give him any encouragement," he said.
