Between them, the two famous clubs have been European champions 11 times - Milan edging Liverpool by six wins to five - but the Merseysiders will be hoping to draw level with their opponents in the all-time list of winners with victory in the Olympic Stadium.
Reds boss Rafa Benitez will be gunning for a second triumph in just three years in charge on Merseyside, while Milan coach Carlo Ancelotti will also be hoping to claim his second gong, following on from the Milan's triumph in 2003.
Ancelotti heads into the game in the enviable position of being able to pick his side from a fully fit squad, but the tactician faces a major dilemma up front, with Pippo Inzaghi and Alberto Gilardino battling it out to spearhead the Rossoneri attack.
With Brazilian Ronaldo cup-tied and compatriot Ricardo Oliveira struggling to find his form since arriving at the San Siro in January, it is a straight fight between the two Italy internationals.
So far this competition, Ancelotti has mostly employed Gilardino at the San Siro, while Inzaghi has been preferred for games away from home. But whoever gets the nod is certain to be led out onto the pitch by Milan skipper Paolo Maldini.
The veteran defender has managed to shake off a niggling knee injury and will play in his eighth final, becoming the oldest player, at 38, to captain a side in a Champions League final.
For Liverpool, winger Boudewijn Zenden had been an injury doubt, but the Dutchman seems to have recovered in time and is likely to be passed fit to play. Benitez said: "He looks like he will be OK, he has trained and I expect him to be fit."
That leaves just Momo Sissoko as Benitez' only injury worry, with the Malian facing a late test to prove his fitness.
With a wealth of midfielders at their disposal, Liverpool are likely to play with just Dirk Kuyt up front, with skipper Steven Gerrard supporting the lone striker from midfield. That means there will be a place in the middle alongside Javier Mascherano for Xabi Alonso, with Zenden on the left and Jermaine Pennant on the right.
Liverpool keeper Jose Reina has been passed fit after injuring a shoulder in the penultimate game of the season and is sure to start.