Costa has scored 21 goals in 26 La Liga appearances, a figure that puts him alongside the legendary Cristiano Ronaldo in terms of efficacy.
At the San Siro, the Atleti striker was the lone scorer in the 1-0 first leg win for the Spanish side, as one defensive miscue from a set piece was enough to give Costa an open header at Milan's goal.
Other than that sole error, Milan did a fine job of containing the naturalized Spaniard throughout the match, as Adil Rami was often given the task of matching his physicality and containing him.
Seedorf's 4-2-3-1 is expected to see both Michael Essien and Nigel De Jong provide the steel in front of the four-man backline.
Both of these defensive midfielders are competent enough to help out the center-backs whenever Costa gets the ball, double teaming him and forcing him to make a play with his feet away from the penalty box.
Expect De Jong to drop back into a center-back position when Milan is under pressure, effectively giving the back line plenty of support considering the fact that the Rossoneri full-backs are not the most capable on the defensive end.
Daniele Bonera is expected to partner Adil Rami, and he could be exposed by either Costa or the much more technical David Villa, who is one of the most feared finishers in world football.
Will Diego Costa score against Milan in second leg?
Bonera has been a mistake-prone defender in recent seasons, never really being used as a starter until Clarence Seedorf came along. Seedorf knows Bonera well from their days playing at Milan, and he has deemed him to be the best partner for the impressive Adil Rami.
In the end, the service coming from the flanks is what could put the most amount of pressure on Milan's defense, as Diego Costa is so prolific in aerial duels.
Fortunately, Milan's weakness of set piece and aerial defending has been improved dramatically by the January transfer window arrival of Adil Rami, so there is hope that a shutout can be achieved.