WHEN THE PATRIOTS RUN

One of the top defenses in the NFL last season presumably got even better with the addition of new head coach Rex Ryan, a defensive whiz adept at drawing up schemes to confuse and bewilder the Patriots during his six-year stint with the Jets in New York. The Bills are generally lauded for their outstanding pass rush, but linebackers Nigel Bradham and Preston Brown, the team's top two tacklers in 2014, are back for another season, and 10-year vet Manny Lawson will play a larger role this year as the strongside linebacker with Brandon Spikes no longer in Buffalo. The Patriots will welcome back LeGarrette Blount this week following his one-game suspension, but uncertainty on the offensive line makes this is a tall task for the running game. Advantage: Bills

WHEN THE BILLS RUN

The three-headed monster of C.J. Spiller, Fred Jackson and Anthony Dixon, monstrous in name only, has finally been disbanded in Buffalo. Spiller and Jackson are gone, and the Bills have a lead back in ex-Philadelphia Eagle LeSean McCoy, who rushed for 1,319 yards last season and has cracked the 1,000-yard plateau four times in six NFL seasons. There are always questions about durability with McCoy, but the bigger question mark is Buffalo's new-look offensive line, anchored by Richie Incognito and rookie John Miller. The Bills have to run the ball successfully in order to win, which won't be easy against New England's front seven, arguably its best in the past 10 seasons. The Patriots efforts up front will be key. Advantage: Patriots

WHEN THE PATRIOTS PASS

There's no denying Tom Brady and his ability to adjust under pressure, but Buffalo's pass rush, led by ends Mario Williams and Jerry Hughes and dominant tackles Marcell Dareus and Kyle Williams, is arguably the best in the NFL. The Bills led the league in sacks in 2014 and return everyone on the front four. Add to that the presence of Ryan in his first year at the helm, and it's a dangerous combination against a New England offensive line playing without injured center Bryan Stork. The Patriots have no choice but to readjust their lineup, which means Nate Solder won't get as much help on the left side as he did a year ago. It could be a field day for Hughes if the Patriots don't come up with a way to add extra protection up front. Advantage: Bills

WHEN THE BILLS PASS

There are still questions about this New England secondary and how it will hold up over the course of the season without Brandon Browner and Darrelle Revis, but Buffalo is no major threat offensively. The Bills have two tremendous weapons in Sammy Watkins, a borderline top-flight NFL receiver, and newcomer Percy Harvin, but no one to throw the ball. Fifth-year vet Tyrod Taylor, who entered 2015 with no more than 29 pass attempts in a single season, beat out former first-round draft pick E.J. Manuel, now third on the depth chart behind former Patriot Matt Cassel. Taylor may be more dangerous with his legs but as a passer he's unproven. With depth at safety and the ability to mix and match coverages, this could be a long day for Buffalo. Advantage: Patriots

SPECIAL TEAMS

Both New England and Buffalo ranked among the top teams in the league in kickoff and punt return coverage last year, but also finished near the bottom in kick return yards. The addition of Harvin in Buffalo gives the Bills a legitimate weapon on special teams. Harvin entered 2015 with five kick returns for touchdowns, two of them during his rookie season with Minnesota in 2009. New England's most effective return man is wide receiver Julian Edelman, who scored his fourth career special teams touchdown last year and remains a game-changer in field position battles. The one equalizer in a close game could be kicker Stephen Gostkowski, one of the league's most consistent at his position and a consistent threat in all weather conditions. Advantage: Patriots

OTHER FACTORS

Division games on the road are always a tall order, particularly in the AFC East, but the Patriots have had tremendous success against Buffalo under Bill Belichick, winning 21 of 23 overall dating back to 2003. The Patriots haven't lost at Buffalo since 2011, but the addition of Ryan adds an extra flair to this already-heated division rivalry. Some of Ryan's best and worst coaching moments have come against New England, from winning at Foxborough in the 2010 playoffs to getting blown out in the infamous Mark Sanchez butt-fumble game in 2012. This might be the best defense Ryan has had at his disposal in years, and he's familiar with the Patriots and their system. The Patriots are just slight favorites, which speaks to the tightness of the matchups. Advantage: Bills