In 2016, a US appeals court upheld a $1bn (£700m) settlement between the NFL and a group of retired players who had suffered brain damage as a result of concussions.
Since then, says NFL chief medical officer Dr Allen Sills, the organisation has instilled a "very aggressive programme to try and reduce those injuries".
In fact, Sills says, the league was able to "reduce concussions by 29%" last year.
"That doesn't mean we have solved the problem but we are moving in a positive direction," he added.
With rugby, football and boxing under the spotlight around head injuries this year, Sills spoke to BBC Sport about what British sports can learn from the NFL about dealing with head traumas and concussion.
Prevention is better than treatment
Sills says a lot of research has taken place over the past five years to identify what is causing concussions, who is being injured and by what type of play.
"We have attacked that over a couple of different fronts," he told BBC Sport.
"We've looked at rules and how that can be applied; we've seen some changes - for example the new kick-off rule, a rule about blindside blocks and the lowering of the head - rules that came directly out of our work around health and safety.
"We have also worked a lot on helmets - the design and the testing of helmets to improve their safety.
"Lastly, we've done a lot with education, specifically for coaches and players, showing them what techniques lead to injury and how alternative techniques may be safer."
He says that league-wide effort has helped reduce the number of concussions being suffered.
"We still have work to do to continue to reduce avoidable head contact," he added.
"In medicine, prevention is always better than treatment."
Spotters in the stands to identify injuries
NFL protocols mean each player gets the same exam whenever they are evaluated for a head injury - anyone deemed to have suffered a concussion cannot return to the field.
The tests, carried out in a pitch-side tent, include a set of simple questions about the game, the location or the player's team, while medics assess the player's eye movement, speech and behaviour.
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"We have created a mechanism whereby many different observers can initiate the protocol," added Sills.
"It can be one of the team medical staff on the sideline, but it can also be one of our spotters up in the booth who are looking for injuries down on the field from an elevated position.
"It can be some of our independent medical personnel on either sideline - doctors, consultants, a player, coach or even game official. All of these people can say 'I think this player should be examined'.
"That has been successful, to allow a lot of people to potentially identify an injured player."
An understanding from coaches and players
Screening of players produces three who prove to have no concussion for every one who does.
"That's a number we're very comfortable with because we want to be as comprehensive as we can be," added Sills, who says this requires continued education and discussion with stakeholders.
"Screening is important - one of the changes I've seen over the past 10 years is players much more readily understand and accept the protocol and why we are trying to do what we're doing, and coaches do as well.
"When one of our players is pulled out to go for a concussion exam, the coach is very hands-off. That's been a cultural change and I think is very positive."
Sharing knowledge with other sports
England rugby union prop Kyle Sinckler saw his World Cup final ended inside three minutes after a collision with team-mate Maro Itoje, highlighting rugby union's strict head injury assessment rules.
Head traumas in football are still a topic being explored; children under the age of 11 playing soccer in the US are banned from heading the ball and the Scottish FA is considering implementing such a rule.
Dr John MacLean, the Scottish FA chief medical consultant, is also part of a Uefa medical committee which has proposed temporary rugby-style substitutions for concussions, after research into dementia in football.
Sills says the NFL is always keen to share information and research with other organisations.
"It is very much a dynamic conversation that is happening on a worldwide basis," he said.
"We want to be very open and transparent about what we have learned and where our challenges remain."
A word on mental health
In May, the NFL announced a new agreement with its players' association to put a renewed emphasis on mental health.
"Part of that new agreement is every one of our 32 clubs has been required to hire a consultant who is at the team facility between eight and 12 hours per week, available to all players and has full access to the entire facility," explained Sills.
"We have put a renewed emphasis on education, and we also recognise how important confidentiality is so have put in some very strict measures around that.
"This is an area we have put a tremendous amount of focus on this year and we think it is something we will continue to emphasise."
It has been well received, with the league keen to promote "a climate of mental wellness" for players and staff.
"A lot of what has driven that is our colleges and universities have been doing it for a couple of years," added Sills.
"Newer players are a little bit more accustomed to it; players who have been around a little time perhaps still have some adjustment.
"Around sports there is sometimes stigma, particularly in football, to be tough and play through injury.
"We spend a lot of time talking about preventing, say, ankle injuries or knee injuries, but there are strategies one can employ to prevent behavioural or mental health issues, so we would like to talk about that rather than mental illness - talk about mental wellness."