For the defender, the moment of truth in stopping the zone-read arrives at the exchange.
Each man has an assignment that seems cut-and-dried, but choosing who to tackle while a play unfolds at NFL speeds can muddle decision making. More than 80,000 fans screaming in unison doesn't help.
When the 49ers travel to FedExField to face the Redskins on Monday Night Football, they bring the NFL's fifth-ranked rushing offense, directed by quarterback Colin Kaepernick, who has the fourth-most rushing yards among quarterbacks.
Redskins linebacker Ryan Kerrigan said at some point in the game, he'll probably tackle his man only to realize the guy with the football is still running.
"It turns into a bit of a guessing game," he said. "Everyone has their assignment, but ultimately, until after the play, you don't know who's got the ball."
A handful of teams proliferated the option offense in the NFL last season, none more prominent than the Washington Redskins.
Led by rookie runners Alfred Morris (1,613 yards rushing) and Robert Griffin III (815 yards), Washington posted an NFL-best 2,709 yards on the ground.
Out of the top-five rushing teams, three had young quarterbacks who were asked to run often in college. The Redskins, 49ers and Seahawks, led by rookie Russell Wilson, heavily employed the zone-read scheme, while the Vikings and the Chiefs were spearheaded by workhorse backs Adrian Peterson and Jamaal Charles, respectively.
That success continues in 2013.
Through 11 weeks, every top-five rushing team has a dual-threat quarterback running the zone-read. Washington is back at the top of the list (155.2 yards per game), while San Francisco (141.0) and Seattle (147.9) are familiar members.
Terrell Pryor leads all quarterbacks with 504 yards rushing, injecting Oakland into the mix. Philadelphia is new to the list thanks to LeSean McCoy, the only back to top 1,000 yards so far this season.
Nick Foles does not possess the raw athleticism of the signal callers form the rest of the group, but the Eagles' quarterback ran for 47 yards and a touchdown against Washington. Chip Kelly's Oregon offense is predicated on the misdirection and confusion of the option.
On Monday Night Football last week, Carolina quarterback Cam Newton ran for 62 yards in a win over the Patriots. The third-year player won the game with his arm, throwing three touchdown passes. Newton ran most effectively on broken plays, but the Panthers still flashed elements of the option throughout.
If nothing else, defenses have to spend time during the week preparing to defend it.
With more than 250 games of experience under his belt, linebacker London Fletcher has seen gimmicks come and go, but recognizes that this is much more of a movement.
"When Cam [Newton] first came on the scene, and you saw what he was able to do, all the numbers he was putting up running the football, throwing the football, it was something unique to the league," Fletcher said. "Now as defenses, you have to pay more attention. You have to spend a little bit more time studying that.
"It's 11-on-11 football now. It's no longer where you can have your safety just sitting back in the middle of the field playing a pass."
Fletcher said defenses have utilized a full year of film in their libraries to improve their stands against the scheme.
Both Griffin III, coming off his second reconstructive knee surgery in four years, and Kaepernick, beginning the season as a starter for the first time, have struggled with consistency.
Griffin III has already doubled his interception total from 2012 by throwing 10 picks. Kaepernick has completed less than 60 percent of his passes in six-of-10 games.
When scouting Kaepernick, the Redskins have the benefit of watching a similar athlete under center at home.
Kerrigan said practicing against Griffin III and the Redskins' first team offense since training camp and OTAs was "good advanced training" for stopping the zone-read.
He also said the team didn't break routine to prepare for the 49ers, and backup Kirk Cousins was still the scout team quarterback.
Whether defenders tackle the ball-carrier or the decoy, the Redskins have the best chance of slowing down San Francisco's zone-read attack if they maintain discipline with their gap assignments.
"You've got to be disciplined, No. 1. He's got great speed," explained defensive coordinator Jim Haslett. "You've got to have somebody that can run him down.
"But he'll run at the drop of the hat. If nothing is open, he turns it up and he's got great speed. So it's a good test for us up front to make sure we stay disciplined in our rush lanes."