Gent face a similar task in tonight’s less glamorous match against Wolfsburg.
But miraculous comebacks do occasionally happen.
Roma’s chance is obviously tougher. The two away goals conceded in the Stadio Olimpico are challenging enough, but in addition they have their talismanic leader Daniele De Rossi injured and their other midfield dynamo Radja Nainggolan has a groin problem.
Without those two, Spalletti’s team look to be extremely vulnerable in defence and some fans fear a drubbing similar to those inflicted by Bayern Munich in last season’s group stage or in their horror show at Old Trafford in April 2007.
Cristiano Ronaldo scored either side of half-time back then and for all Madrid’s troubles this season he is a man on a mission.
Yet Roma and Spalletti know that they had their chances in the first leg. They might have had a penalty, and their pace on the break, particularly the speed of Mohammed Salah, worried the Spanish.
The Egyptian winger is in great form and was man of the match in the 4-1 thrashing of Fiorentina. Stephan El Shaarawy — Italian, but with an Egyptian father — opened the scoring with his fifth goal since he arrived on loan from Milan in January.
Cue lots of headlines about Pharaohs.
Spalletti also has the tactical intelligence to surprise Zinedine Zidane’s side.
He’s one of Italy’s more daring managers — his thesis when he did his coaching badges was on the advantages of playing 3-4-3 — and above all he has always believed that attack is the best form of defence.
He was in charge when Roma beat Madrid 2-1 home and away at the same stage of the tournament in 2001, helped by a red card for Pepe in the second leg, which was also at the Bernabeu. Then too Spalletti had speed on the wings, with Francesco Totti operating as a withdrawn striker.
Totti is still around of course, although his presence can be more of a hindrance than a help. The club are trying to persuade him to end his playing career — he turns 40 in September — and Spalletti is probably the one man who can do it.
“I hope he closes his career in the best way, listening to what his heart tells him,” Spalletti told Roma TV.
“Undoubtedly, my role becomes difficult in this situation, but I have absolute respect for the man and his career.”
But the fans are not happy about losing their most famous player.
Zidane has wisely told his players that this match is not a foregone conclusion — a warning directed as much at the fans as the team.From personal experience he knows that the mood at Madrid can turn sour very quickly.
He had a relatively straightforward introduction to management following the departure of Rafael Benitez, but like Rafa then suffered a home defeat in a critical game, 1-0 in the derby against Atletico.
It has left them scrapping for second place, nine points off the lead.
Ronaldo is the key of course, and his fusillade gainst Celta Vigo in the second half on Saturday, with four goals inside half an hour, shows that he can demolish most sides.
Admittedly Celta are not good at defending — they’ve now conceded 51 goals, just one fewer than La Liga’s bottom club Levante — but on home turf Ronaldo is still a player who can genuinely rival Barcelona’s main men.
Tonight’s other tie is a huge opportunity for Wolfsburg.
Gent would already be out but for the two goals they grabbed at the end of the first leg when the Germans lost concentration.
At 3-2 up they must be favourites, but they have three injured and another three who are carrying injuries, among them their form player Julian Draxler.
Both tonight’s matches should produce a lot of scoring chances.
Roma have nothing to lose, although Spalletti has stressed that they need to pick their moments.
For both Wolfsburg and Gent this is a chance to advance into unknown territory.
Whatever the money-men may say, it is good for the competition to have new teams reaching the quarter-finals.