Kickoff is scheduled for 1 p.m. Sunday in Buffalo. Here are five keys for the Panthers:
Rattle the rookie: Buffalo quarterback EJ Manuel held his poise in his first start against New England, completing 18 of 27 pass attempts for 150 yards and two touchdowns. He also didn't throw an interception and wasn't sacked. Carolina won't throw many blitzes at Manuel, believing it can get solid pressure out of its front seven. But the Panthers have to get to Manuel more often than they did Seattle's Russell Wilson, who despite being sacked twice and pressured countless times scrambled around long enough to complete 76 percent of his passes for 320 yards.
Three and out: Buffalo struggled to move the chains with its up-tempo offense against New England, collecting only 15 first downs in the 23-21 loss. The Panthers must find a way to do the same, and it begins with stopping the run against a somewhat conservative offense designed to keep pressure off its young quarterback. Buffalo had 136 yards rushing in Week 1, which enabled it to play the Patriots close. Carolina needs to keep that total closer to the 70-yard range it held Seattle to.
Going deep: Much has been made of Carolina attempting only three passes of more than 10 yards against Seattle. Too much. Do the Panthers need to take a few shots down field just to open things up? Yes. But simply finding a way to get the receivers more involved will be the bigger key. Outside of Steve Smith (6 catches, 51 yards), Carolina wide receivers had one catch. Look for Domenik Hixon, Armanti Edwards and Ted Ginn Jr. to be more involved against a banged-up Buffalo secondary that could be missing two starters. Also look for quarterback Cam Newton to take a few more shots down field with his running.
Point of attack: It all could boil down to this for the Panthers. Can their offensive line with Amini Silatolu back at left guard control a Buffalo defensive front that will throw a variety of blitzes as them? The best way to do that is establish running back DeAngelo Williams as they did last week when he had 86 yards rushing against a tough Seattle defense. Some of those 3- and 4-yard runs could turn into 6 or more if the Panthers eliminate little mistakes.
Hold on to the ball: It's really simple. Had DeAngelo Williams not fumbled at the Seattle 8-yard line in the fourth quarter and had tight end Greg Olsen not dropped two passes (both that would have gone for big yardage), Carolina might not be staring at a potential 0-2 start. Good teams can overcome these kind of mistakes. The Panthers haven't reached that status.