As ever, it has been a busy off-season, with a number of issues dominating the headlines in the five months since the Patriots lifted the Lombardi Trophy for the fourth time.
Sports Mole takes a look at some of the talking points heading into the new season.
The so-called 'deflategate' scandal has been the big story over the summer, with the New England Patriots found to have let air out of their footballs during their run to last season's Super Bowl, making the balls easier to grip and throw.
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As a result, quarterback Tom Brady was handed a four-game ban, while the team was given a fine, but after an appeal the two-time league MVP had his suspension overturned, ensuring that he will be available for tonight's opening game.
The league has been keeping a closer eye on ball pressures during pre-season games, with gameballs now being marked numerically to make them easier to check, so it is something that is likely to be monitored through the coming season.
2. Off-field behaviour
What NFL players get up to when they are away from the football field has always made news, but with Ray Rice's domestic violence case and Adrian Peterson's suspension for child abuse was season, the behaviour of players during the off-season has been under scrutiny more than ever.
Cleveland Browns quarterback Johnny Manziel heads into this season fresh from a stint in rehab for alcohol problems, having missed a team meeting towards the end of last season after reportedly hosting a party the night before.
There were also a couple of incidents on July 4 involving players and fireworks. New York Giants defensive end Jason Pierre-Paul lost his right index finger after having an accident with a firework, while Tampa Bay Buccaneers cornerback CJ Wilson was forced to retire after losing two fingers in a similar incident.
The risk of concussion is an occupational hazard for NFL players, despite them wearing helmets and the league having a strict protocol in place for players who take hits to the head.
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San Francisco 49ers linebacker Chris Borland had a promising rookie campaign with the NFC West side in 2014, but announced his shock retirement in March, citing concern of the effects of concussions. The 24-year-old, who repaid over $400,000 (£260,000) of his signing bonus, was due to make $500,000 (£325,000) in his second season, but decided that it was not worth the risk.
Over 70 former NFL players have claimed to be suffering the effects of chronic traumatic encephalopathy; a condition which arises from repetitive brain injuries. The illness can only be definitively diagnosed post-mortem, but a study which examined the brains of 34 deceased NFL players found that 33 had signs of CTE. Over 4,500 players have reached settlements with the NFL over the suffering of concussions.
4. NFL in the UK
For the second year in a row, three NFL regular season games will take place at Wembley, while Tottenham Hotspur have announced plans to accommodate NFL games in their new stadium.
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Such developments have led to growing talk of London securing its own franchise. Fulham owner Shad Khan also owns the Jacksonville Jaguars, who will be playing at Wembley for the third time this year. His commitment to bringing the team to London has led to speculation that he could relocate the franchise in the future.
Two-time Super Bowl winner Osi Umenyiora, who was born in London, retired from playing this summer, but will spend the next six months working as an ambassador for the NFL in the UK. However, he has also said that he would like to be the general manager of the first London NFL franchise.
5. Super Bowl 50
The aim of every team heading into the new season is to reach the Super Bowl, and that will be no different this year with the 50th edition of the championship game taking place at the 49ers' Levi's Stadium. As it is the 50th time the Super Bowl has been held, and it is taking place in California, the game has been dubbed the Golden Super Bowl.
Last year's beaten finalists the Seattle Seahawks are among the favourites, having reached the last two championships games, while the Green Bay Packers and Indianapolis Colts are also hotly-tipped to do well this year. Meanwhile, the Jacksonville Jaguars and Oakland Raiders are among the rank outsiders.
The Steelers, Patriots and Dallas Cowboys have more Super Bowl appearances than the other sides in the NFL, each reaching the game eight times. The Steelers remain the most successful with six wins.