The Bills showed perseverance and determination last Sunday against the Cincinnati Bengals, coming away with a 49-31 victory, despite trailing 31-14 at the half.
The Bills are looking to win three games in a row for the first time since beginning the 2008 season 4-0, while the Steelers are looking to take control of the AFC North division lead.
As always, let's take a look at the top individual player vs. player matchups that will determine the outcome of what should be an exciting game to watch.
While Steelers outside linebacker James Harrison has made headlines for his fine-inducing helmet-to-helmet hits throughout the 2010 season, his outstanding play has been vastly overshadowed.
Harrison has racked up 69 tackles, three tackles for a loss, nine sacks, while defending four passes, forcing five fumbles, and intercepting two passes on the year.
He will line up against Bills left tackle Demetrius Bell, who is maturing into a decent pass protector in his first season as a full-time starter.
Bell has his work cut out for him this week, and while he has the length and strength to contain opposing pass-rushers, he has struggled against 3-4 defensive fronts, in which he takes on rushing ‘backers, as well as defensive ends.
The Steelers have the best run defense in the National Football League, allowing just 64 yards per game on the ground, thanks to the outstanding play by veteran James Farrior and youngster Lawrence Timmons.
Timmons leads the Steelers in tackles, with 89, and has added three sacks, six tackles for losses, eight pass defenses, two interceptions and a forced fumble, while Farrior has racked up 70 tackles, two sacks, three tackles for losses, and a forced fumble.
Jackson has been on a roll as of late, and has rushed 129 times for 562 yards on the year, finding the endzone five times, but he will have a tough challenge ahead of him on Sunday.
Jackson will need help from his fullback, Corey McIntyre, to carry out his lead blocks, as well as his interior linemen to create space.
Steelers CB Bryant McFadden Vs. Bills WR Stevie Johnson
Stevie Johnson has had a breakout year, catching 52 passes for 728 yards, and nine touchdowns, and will certainly have some opportunities against a Steelers pass defense that has allowed 239 yards per game through the air.
Bryant McFadden is a physical corner that has the strength to jam Johnson at the line of scrimmage, but Johnson's performance will depend on the ability of Bills quarterback Ryan Fitzpatrick getting the ball out of his hand quick enough.
McFadden has 63 tackles on the year to go with his two sacks, and has defended seven passes while intercepting one.
The Steelers often bring the heat from both the strong and weak sides, which could present a challenge for the inexperienced right tackles Cordero Howard and Mansfield Wrotto, who have been used in a rotation recently.
LaMarr Woodley has been wreaking havoc on right tackles all season long, racking up 32 tackles, 6.5 sacks, three defended passes, an interception, and has forced three fumbles.
Steelers S Troy Polamalu Vs. Bills QB Ryan Fitzpatrick
Troy Polamalu is a player that needs to be accounted for before, during, and after every play that takes place on the field. He is a game changing safety that seemingly knows what is going to happen before the play develops.
On the season, Polamalu has 52 tackles, four for a loss, four defended passes, and three interceptions.
With all the pressure the Steelers will be bringing on Ryan Fitzpatrick, Polamalu will have multiple opportunities to execute his game-changing ability.
Fitzpatrick, who is having the best season of his career, completing 59.3% of his passes, throwing for 1,961 yards, 18 touchdowns, and nine interceptions, has thrown some costly interceptions throughout the year, especially late in games that resulted in losses for the Bills.
Mike Wallace is a speedster and is an explosive wide receiver that can score on any play. With Terrence McGee suffering nagging injuries to his leg, Leodis Mckelvin will most likely be lined up with Wallace on Sunday, to keep his speed in check.
Wallace has caught just 33 passes this season, but eight have been for scores, and have resulted in 759 yards, for an average of about 23 yards per catch.
Leodis Mckelvin has been getting better and better each week, but to stop Wallace, he will need to jam him at the line of scrimmage, and shade a safety over the top (maybe Jairus Byrd can snag one!).
The Steelers have a banged up offensive line, with tackles Willie Colon and Max Starks on injured reserve, but running back Rashard Mendenhall should be set for a great performance against the Bills worst ranked run defense, that has allowed 164 yards per game on the ground.
Mendenhall has rushed 202 times for 811 yards; scoring eight times, while adding 16 receptions for 98 yards out of the backfield.
Paul Posluszny has been a force in the run game for the Bills, recording 88 tackles, two for a loss, and a sack, despite appearing in just eight of the ten games this season.
Steelers C Maurkice Pouncey Vs. Bills NT Kyle Williams
Kyle Williams was expected to see a significant drop not only in his individual statistics, but his personal play as well this season, due to the transition from the defensive tackle position to the nose tackle, which requires taking on a double team, and acting as a "space eater."
However, his outstanding play has thrust him into Pro Bowl discussion, and has been ranked higher than in-division rival nose tackle, Vince Wilfork, of the New England Patriots, in terms of defensive tackles.
Williams has recorded 50 tackles, seven tackles for a loss, and three sacks, and has displayed strength to collapse the pocket, and shed multiple blockers at once.
He will line up against rookie center, Maurkice Pouncey, who was drafted out of Florida, and has been solid in his first year in the National Football League.
It has been no secret that the Buffalo Bills defense against opposing tight ends has been dreadful, mainly due to the transition from the 4-3 front to a 3-4, which has left most players in new positions.
Chris Kelsay has been the most visible of the struggling Bills, which has forced the Bills to play safety Bryan Scott at linebacker, while using safeties to keep an eye on tight ends. Against tight ends, the Bills have collectively allowed 32 receptions for 501 yards and eight touchdowns through the first ten games of the year.
Heath Miller has caught just 28 passes for 329 yards and scored a touchdown this year, but Steelers coach Mike Tomlin definitely knows that defending tight ends has been a weakness of the Bills, and he will try to take advantage of that as often as possible.