1. Keep Tom Brady clean. It goes without saying, but Brady is the Patriots' primary ticket to their championship hopes. He's taken some big hits in recent weeks and will be playing with a sore left non-throwing shoulder, so they must keep him out of harm's way.
2. Avoid the turnover trap. In the Sept. 25 meeting between the teams, Brady threw four interceptions. As Brady said this week, a team isn't going to win many games when a quarterback throws four picks. The Patriots had 14 turnovers in their first eight games, but just two in their past seven, which has been a key in their resurgence.
3. Don't let C.J. Spiller become a big factor. One of the Bills' best chances to win would be if Spiller gets going on the ground or as a pass-catcher. Special attention figures to be paid to him in both areas.
4. Answer the challenge on special teams. The Bills always seem to be dangerous in this area, whether it's blocking kicks or running back punts and kickoffs. With top special-teams coverage man Tracy White (questionable, abdomen) possibly not playing for the Patriots, others would have to emerge.
5. Bring the heat on Ryan Fitzpatrick. While opponents haven't had great success sacking Fitzpatrick, the Patriots want to at least create stress in his decision-making process, yielding a better chance to generate turnovers. Look for some pressure in this game.
Mike Reiss covers the Patriots for ESPNBoston.com.