After an expected 2-1 start, Chan Gailey's club has lost five of six, including a crushing last-second defeat at the hands of the New England Patriots in Week 10.
At 3-6, they're clinging to faint playoff hopes, but with the vast mediocrity that's spread across the entire AFC, they aren't giving up on their season just yet.
They have to start what would be a magical run at the postseason by upending the 4-5 Dolphins in front of their home crowd this evening.
Here are the individual matchups Buffalo has to win to emerge victorious in front of a national TV audience.
(slides listed by order of importance)
C.J. Spiller is an emerging NFL star, and tonight he has the opportunity to morph his budding fame into legitimate superstardom.
His 7.3 yards-per-carry average is the highest in the league and is 1.5 yards higher than the running back with the second-highest average, Adrian Peterson.
This isn't a fluke, either.
The 2010 first-round pick has accumulated at least 100 total yards from scrimmage in four straight games and in 10 of his last 14 outings.
He is arguably the most explosive player in the NFL right now.
Tonight, he's up against one of the league's more stout run defenses.
Miami has allowed the fifth-fewest rushing yards (848) and the third-fewest yard-per-carry averages (3.8) this season.
However, last week Tennessee Titans' running back Chris Johnson went for 126 yards at a 5.5 yards-per-rush clip, and as a team the Dolphins have surrendered 135.25 rushing yards per game and 4.87 yards per carry in their last four contests.
With Fred Jackson out with a concussion, many believe Spiller will finally receive the amount of carries he deserves.
Buffalo's coaching staff has to feature the speedy runner as prominently as ever before—he's never been given more than 19 carries in his career—and Spiller must wear down Miami's run defense to keep the Bills offense on the field and, ultimately, into the end zone.
Currently, the Buffalo Bills have the NFL's worst run defense.
The numbers aren't lying.
To date, they have allowed the most total rushing yards (1,473), yards per carry (5.5) and rushing touchdowns (16) this season.
The run defense is fresh off of a relatively respectable effort against the New England Patriots in Week 10, when Stevan Ridley and Co. mustered only four yards per rush en route to a 117-yard afternoon.
Miami's running back stable of Reggie Bush, Lamar Miller and Daniel Thomas hasn't been necessarily potent in 2012, but they aren't a totally deficient group.
As a team, the Dolphins average a rather paltry 3.8 yards per rush, but Bush and Miller certainly possess breakaway talent.
For the overwhelming majority of the year, Buffalo's defense—not its offense—has been the problem and, most specifically, the inability to stop the run has made it exceedingly difficult for Ryan Fitzpatrick's attack to keep the Bills in games.
Although the high-priced defensive line has taking an abundance of criticism, the linebacking play has been the defense's most glaring weakness.
Nick Barnett is active, but he has been caught out of position when attempting to fill running lanes on some of the big-gainers Buffalo's allowed.
The same goes for middle linebacker Kelvin Sheppard, a player who flashes potential, then takes the wrong angle on what eventually becomes a huge run play for the opposition.
The play of those two second-level defenders will be key this evening.
Cameron Wake burst onto the scene in 2010 when he totaled 14.5 sacks.
Then, with opposing offensive lines focusing their game plans on stopping him last season, he mustered only 8.5 quarterback takedowns—still a respectable number.
Thus far in 2012, he already has accumulated 8.5 sacks and has been a terror on the edge of the Dolphins 4-3 alignment.
It is worth noting, however, that a whopping 4.5 of those sacks came against the beleaguered Arizona Cardinals front.
He's a supremely-gifted outside rusher with good speed, strength and a high motor.
For rookie left tackle Cordy Glenn, he'll be a formidable matchup.
Returning from an ankle injury last week against the Patriots, Glenn handled fellow rookie Chandler Jones relatively well after he started off the game looking a bit sluggish.
Like most quarterbacks, Ryan Fitzpatrick is much more accurate and effective when he's afforded a clean pocket, and Glenn has to win his matchup with Wake to keep the Bills as efficient as possible on offense.
Oh, Ryan Fitzpatrick.
The ultra-polarizing, controversial and, during his time as the Bills' starter, inconsistent quarterback.
It's easy to pile on Fitzpatrick due to his seventh-round draft status, visibly weak arm and sporadic play—I get it.
But, I've attempted to avoid simply joining the masses before ridiculing Buffalo's signal-caller.
I've watched—and re-watched—every throw the Harvard alum has made this season, and I've come to this conclusion.
He's clearly not the future for the Bills, but right now, Buffalo can't worry about that.
But he is good enough, in Chan Gailey's system, with C.J. Spiller in the backfield and a steady offensive line in front of him, to lead his club to the playoffs.
(That comment made notwithstanding Buffalo's defensive woes.)
QB rating is far from the end-all-be-all when it comes to analyzing the success of a quarterback, but if his rating was embarrassingly low, wouldn't people be quick to point it out?
Over the last three games, he's completed 69.9 percent of his passes at 267 yards per game with five touchdowns and two interceptions.
The Dolphins secondary has floundered of late, and Luck set the single game rookie record with 433 passing yards just two weeks ago.
Currently, Miami has allowed the seventh-most aerial yards (2,502), but opposing signal-callers average the ninth-lowest QB rating (80.1).
Spiller will presumably be the focal point of Buffalo's offensive attack, but Fitzpatrick has to be efficient against a susceptible—but not horrid—Dolphins defensive backfield this evening.
Stevie Johnson will have an impact on tonight's AFC East clash, but watch for Buffalo's tight end, Scott Chandler, to be an even more integral component of what the Bills try to do on offense.
At 6'7'' with deceptive speed and a clear rapport with Fitzpatrick, Chandler has to be utilized often and get open with Miami's linebackers in coverage.
In the two games he's received eight targets this season, he has reeled in a total of nine passes for 127 yards with three touchdowns.
No, he's not a gamebreaker like Jimmy Graham or Rob Gronkowski, but he's a huge, chain-moving target that runs crisp routes and can stretch the field down the seam.
Of his 27 receptions, 23 have gone for first downs.
Believe it or not, that's the best reception-to-first down ratio among tight ends this season.
Though Chandler isn't overly flashy, he creates a mismatch nearly every time he runs a route and has to "win" his individual matchup with the variety of cover men Miami will send his way tonight.