Job One for the Bears' defense Sunday will be containing the combination of Fred Jackson and C.J. Spiller, which gives the Bills one of the NFL's most potent rushing attacks.
Spiller rushed for 933 yards and averaged 4.6 yards per carry last season, while Jackson ran for 890 yards and averaged 4.3 yards.
Together they helped the Bills finish No. 2 in rushing yards.
Although he's 33, the 6-foot-1, 216-pound Jackson gave little indication last year that he was in decline, an affliction that has struck most running backs after age 30.
Although Jackson had 9 touchdowns last season, Spiller has the instant acceleration and top-end speed to threaten the end zone on every carry.
According to right end Jared Allen, every Bears defender must be gap sound, especially himself and left end Lamarr Houston.
In the Bills' zone-read offense, the running back is often reading what the defensive end does to determine his course.
"Me or Lamarr, the D-ends are the read guys," Allen said. "But we all have responsibilities within the defense. If we take care of them, be fundamentally sound, we'll be all right. Especially with a team like the Bills, if you're out of your gap, that's what they look for.
"Guys like Spiller and Jackson, they're so quick that if you get out of your gap one second, they can jump, stop, cut and be right back in your gap full speed in no time. It's just going to be disciplined football. We've got to tackle."
After missing the entire preseason with a foot injury, right tackle Jordan Mills has the unenviable task of facing Buffalo Bills defensive left end Mario Williams on Sunday.
Williams' 13 sacks were fourth in the NFL last season, so Mills might need some help from tight ends or running backs chipping at the 6-foot-6, 292-pounder.
"I've known Mario for a long time," Bears coach Marc Trestman said. "He was at N.C. State when I was there. He's a difference-making player, no doubt about it. His size, his length, his speed, athleticism, that's all part of it.
"When we look at the Bills' defense, we know we've got to neutralize him. So it just won't be Jordan's responsibility.
"It'll be our entire offense's responsibility to make sure that we do whatever we can to keep him from making those types of plays that can be difference-making plays in a game."
Forget about it:
Defensive end Jared Allen says the Bears' struggles on defense last season mean nothing.
"I don't care what they did last year," said Allen, who was with the Minnesota Vikings in 2013. "It's a totally different team. The NFL, it's 'What have you done for me lately?'
"If we sit back and harp on what happened last year and go back and judge players that aren't even here (it doesn't make sense).
"You look at the injuries alone, that is a major excuse for it. You've got to push forward."
There could be as many as six new starters on defense compared to the 2013 season opener and as many as eight compared to the season finale in 2013.
Last year's defense allowed 478 points, the most in team history.
Safety Chris Conte (concussion) and center Brian de la Puente (knee) were full participants in practice, while fullback Tony Fiammetta (hamstring) remained limited.