1. It is now a delay of game penalty if a team is erroneously granted a timeout.
2. The offensive and defensive play callers can use the coach-to-helmet communications system regardless of whether the coach is in the booth or on the sideline.
3. There is no longer a five-yard penalty for illegally touching a pass after being out of bounds and then re-establishing inbounds, but it is a loss of down.
4. The line of scrimmage for extra point kicks is permanently the 15-yard line.
5. Touchbacks on kickoffs are now moved to the 25-yard line.
6. All chop blocks are illegal.
7. The horse-collar tackle rule now includes a defender grabbing the jersey at the name plate or above.
8. A player who gets two fouls for certain kinds of unsportsmanlike conduct is automatically ejected.
9. Multiple spots of enforcement for a double foul after a change of possession have been eliminated.
The full 2016 rule book is available as a PDF here.