Will Lionel Messi have a say in where the three points are headed?
The last time the Catalans were in town, they left with their tail between their legs, as Kevin Prince-Boateng and Sulley Muntari handed Barca a 2-0 defeat.
It was a game that many thought was the beginning of the end for Barca, yet the way in which they turned the tie around and utterly demolished Milan by four in the return was simply breathtaking.
It's hard to imagine the Rossoneri taking the game to their visitors this time, as they have endured a stuttering start to their Serie A season. Just three wins, all at home, see the home side in a lowly eighth position in the table.
The club have been beset by an injury crisis and, as Harry West reports for Goal.com, Milan will be missing two of their highest-profile players in striker Mario Balotelli and keeper Christian Abbiati for the visit of Barca.
Barcelona had their first "blip"—if we can call a goalless draw away against perennially tough opponents a blip—over the weekend, as Osasuna showed Milan the way with a hard-working and dogged performance.
It may be just that style of Italian defensive play that could see Milan take at least a point from this one.
On current form, standing toe-to-toe with Barca is likely to see a similar result to the thrashing they received in last season's return.
One thing is almost certain. Milan hands will be full with the dual threat of Neymar and Lionel Messi. The Brazilian has offered much in Messi's absence and the speed with which both strikers can break will test the resolve of Philippe Mexes, Cristian Zapata et al.
Rested for the trip to El Sadar, Alexis Sanchez can expect a recall. His knowledge of Italian football through his time at Udinese will be invaluable as he looks to help unpick the lock.
Tata Martino has been rotating more times than a helicopter propellor, but this is precisely the sort of game for a settled and full-strength side.
Andres Iniesta's poor form of late suggests a spell on the sidelines might do him some good. Assuming he prefers not to be dropped, then he will need to wake up and smell the coffee...quickly.
He has flattered to deceive on a number of occasions this season and was simply awful against Osasuna. This game gives him an immediate chance to rectify matters.
Pass master Xavi continues to illuminate. During the match against Levante at the beginning of the season, Xavi had out-passed the entire opposition by half-time. By match's end, he was only six passes worse off!
His astonishing accuracy and talent shine through in every game, so expect him to dictate the pressure from the outset.
Although Alex Song is staking a reasonable case for semi-permanent inclusion in the Barca midfield, there is no reason to suggest that Martino will go with anyone other than the dependable Sergio Busquets in the defensive midfield position.
Muntari and Antonio Nocerino will provide supplementary attack for the hosts, with Nigel de Jong a much more combative presence. Busquets' cautionary work ethic is therefore the right choice.
Defensively, Martin Montoya did himself no favours whatsoever at right-back against Osasuna. Unless he is injured, Dani Alves will without question step straight back into the breach on the right-hand side of the back four.
Adriano Correia keeps his place on the left unless Martino goes for a slight change of tack.
Marc Bartra has proven himself to be a steady and accomplished central defender in Javier Mascherano's absence with a string of high-class performances. Perhaps doesn't deserve to be the fall guy on the basis that those returning from injury have more experience.
If Martino goes with Bartra, expect him to be partnered with Gerard Pique. After being rested for the Osasuna game, we should see a fully refreshed and focused Pique out on the pitch.
That's because old warhorse Carles Puyol is back in town!
Puyol will slot in on the left to accommodate Bartra, but will want to revert back in the centre of defence in the longer term. Three into two doesn't go, so Pique is another that needs to significantly up his game.
MILANELLO - TRAINING UNDERWAY, KAKA' TRAINING WITH GROUP http://t.co/KblI4yJTlN— fans.ac.milan (@fans_ac_milan) October 20, 2013
Due to Balotelli's injury, we may see an early introduction of Kaka, yet the former FIFA World Player of the Year doesn't instill the same fear as he once did and should be contained fairly easily.
Victor Valdes continues in goal and the Milanese will be hoping for a bounce-back performance following the pedestrian way in which he coasted through 90 minutes at El Sadar.
Should Barca triumph, it puts them in the box seat for qualification from the group stages, so expect an exciting and attacking Barcelona performance.