Here are two players from each club that are going to have to step up the biggest in order to pick up three points for their side.
1. Yaya Toure
Toure might be the most important player on Manchester City.
Toure can shut down opposition midfielders and help to begin City attacks from the back. He flies around the entire pitch.
His month off at the African Cup of Nations really negatively affected City.
Frank Lampard and Raul Meireles can break this game open for Chelsea.
Despite his squabbles with Andre Villas-Boas, Lampard has been very good this season. Meireles brings a creative quality that other Chelsea midfielders lack.
If the Citizens are to marginalize those two, Toure has to have a big performance.
2. John Terry
Conversely, it's probably going to be Terry's job to ensure Aguero has little opportunity in front of goal.
He's probably the one player who has benefited the most from the removal of Villas-Boas as Chelsea manager.
Terry struggled mightily in the defensive, high-line system the Portuguese manager deployed. Now with Roberto Di Matteo at the helm, he can focus on doing what he does best, which is sitting very close to goal.
Terry is still a very dependable defender when he's not asked to chase down opposition strikers.
Chelsea will also be looking to utilize his ability in the air on set pieces.
3. Didier Drogba
This is a bit of a toss-up between Drogba and Fernando Torres, but the advantage goes to the Ivorian.
When watching Chelsea's Champions League match with Napoli last week, it was hard to believe that Drogba is 34 years old.
He is able to retain the physicality that has made him so successful over the years.
It hasn't exactly been a been a banner year for Drogba, but it was clear to see that he clashed with AVB, who looked to start phasing him out.
Di Matteo will be looking to the Chelsea veterans like Drogba and Terry to have the biggest impact on the pitch against City.
4. Sergio Aguero
The Carlos Tevez saga should be plenty of evidence to show the perceived striker problem at City.
Despite spending hundreds of millions of pounds, the squad only has three first-choice strikers, one of which, Mario Balotelli, is pretty unstable.
Aguero has had a very good debut season in England. He leads City in scoring with 16 league goals.
You obviously can't win a match without scoring any goals.
It's going to be interesting to see how Roberto Mancini sets up City, although it's doubtful that he'll put them out on the attack.
If Aguero can get behind either John Terry or Gary Cahill on the counter, he's going to be very dangerous.