After a year out of Europe's top club competition, the Giallorossi are back in the Champions League - hosting Atletico Madrid at the Stadio Olimpico.
The Spanish side have been one of the most successful sides in the tournament over the last few seasons - they will surely provide a reminder of just what this competition is all about...
After the weekend game against Sampdoria was postponed due to adverse weather conditions, the Giallorossi have still only played two games this season - opening the campaign with a hard-fought 1-0 away win against Atalanta, before succumbing to a 3-1 defeat at home to Inter Milan at the end of August.
Atletico Madrid have played three games - all of them away from home, as work is completed on their impressive new stadium. Simeone's side have opened with two draws and a win, beating Las Palmas 5-1 but being held by Girona (2-2) and, at the weekend, Valencia (0-0).
They certainly have pedigree in this competition, however - reaching the final in both 2014 and 2016 and making another run to the semi-finals last season.
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Roma will be without new signing Patrik Schick, who picked up a slight thigh knock on Friday, and young full-back Nura Abdullahi, who has a longer-term problem. Full-back Rick Karsdorp, still recovering from knee surgery in the summer, is also not included on this occasion by coach Eusebio Di Francesco.
Both Emerson Palmieri and Leandro Castan are not registered for this phase of the competition.
Di Francesco has more options elsewhere, however, with Alessandro Florenzi and Bruno Peres both fully available after missing the last game against Inter Milan.
Atletico Madrid have a settled squad and rested one too - with Diego Godin, Jose Gimenez and Sime Vrasaljko all available to Diego Simeone after being rested at the weekend.
Forward Antoine Griezmann is also fresh and available after serving a suspension in La Liga.
Eusebio Di Francesco: "Simeone’s side have a very clear identity. It’s less attractive, more practical, but it always achieves results. They’ve reached two Champions League finals and that’s not somewhere you get by chance. They have great mental and physical attributes. In order to compete with them, we’ll need to match their style while staying true to our football identity."
Diego Simeone: "We mustn't mix up our feelings with our jobs. I respect Roma and I have fond memories of my time at Lazio but I'm not a big one for talking now. I'm more interested in looking at how Roma play and they play some excellent stuff. They have some great players, pacy players and a very strong and skilful midfield unit. That's all I'm thinking about now.”
For a period in the summer, it looked like Antoine Griezmann's productive spell at Atletico was coming to an end. But, after signing a lucrative new contract, the Spanish side will now be hoping to ride their talented attacking dynamo to another long run in this season's Champions League.
Griezmann has been involved in 50% of Atletico's goals in the competition over the last two seasons (scoring 13 of them), which is about all the evidence you need of his importance to their attacking play.
Capable with either foot and as dangerous with space 25 yards out as he is from inside the penalty box, Griezmann's combination of vision, technical quality and eye for goal often mean he is the individual talent that elevates the collective strength of Atleti to a higher plane.
If Roma can stop Griezmann, they will quiet Atletico's biggest danger. That is easier said than done, however.
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Clearly this is not a game where one man can do it all - if Roma are to get off to the start they want, then all areas of the team will have to contribute. But the defence, freshened up from last season, will have to be particularly stable - and Kostas Manolas will have a key role to play in that regard.
Now undoubtedly the leader of the back four, Manolas will be tasked with marshalling the defence and keeping a lid on the movements of both Fernando Torres and Griezmann.
The Greece international has traditionally seemed to up his level for the biggest games and the biggest stages and, at his best, is undoubtedly one of the finest and most uncompromising stoppers in the game.
The Giallorossi faithful will be hoping he produces that sort of form on Tuesday night.
Coach Eusebio Di Francesco's major decision comes at right-back, with both Bruno Peres and Alessandro Florenzi back to availability (after layoffs after different lengths) after missing the club's last competitive game.
That could mean Juan Jesus - an emergency right-back against the Giallorossi - shifts into a more familiar role.
Atletico, meanwhile, have a familiar style and - thanks in part to the summer transfer ban - a familiar list of personnel.
"The formation will be a classic 4-4-2, which the Argentine has firmly embedded in the minds of his players by now," says Cristina Cubero from Spanish sports daily Mundo Deportivo. "Oblak between the sticks, Godin and Gimenez in central defence, and Juanfran and Hernandez most likely at full-back.
"Saul, Gabi, Koke and Carrasco will make up the midfield, and up front Griezmann, making his return from suspension in the league, will probably play alongside Torres."
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