Both teams are coming off blowout losses in Week 1 and the Chiefs are looking to exact a bit of revenge from last year's season-opening 41-7 loss to the Bills in their own home stadium.
While the Chiefs certainly shouldn't take the Bills lightly, there has to be a sense of relief going into the game with a handful of key players returning to lineup this week.
Outside linebacker Tamba Hali is back from a one-game suspension, and cornerback Brandon Flowers was a full participant at practice for the first time in over a month and could see the field for the first time all season.
However, Buffalo will be without top running back Fred Jackson after he went down with a knee injury in last week's 48-28 loss to the New York Jets.
Though Jackson vows to be back in four weeks, the Bills will have a chance to see exactly what they have in CJ Spiller. After rushing for 169 yards and one touchdown, Spiller might just buy himself more playing time even when the Bills return to full strength.
Here is one bold prediction for each team in Sunday's matchup:
Tamba Hali and Justin Houston Combine for Four Sacks
After coming on strong to end the 2011 season, Houston is widely seen as the complement to Hali that the Chiefs have been looking for since moving to the 3-4 defense prior to the 2009 season.
This Sunday could be the pair's coming out party.
Hali will be ramped up after missing the team's first game due to violating the league's substance abuse policy. With two capable pass-rushers coming off the edge, the Chiefs' defense will do a much better job of pressuring Bills quarterback Ryan Fitzpatrick than they did against the Falcons last week.
Steve Johnson Finds the End Zone Twice
With Jackson out of the lineup and Spiller being more of a versatile threat out of the backfield, the Bills could find themselves throwing the ball more in the coming weeks.
If Chiefs cornerback Flowers makes his way back onto the field this weekend, Steve Johnson should get plenty of opportunities with the Bills trying to see just how ready Flowers is for live game action.
If Flowers doesn't play on Sunday, however, Fitzpatrick would do well to find Johnson wherever he is on the field, as the Chiefs don't have another cornerback capable of covering the wide receiver.
Either way, Johnson should get his on Sunday.