The quarterback battle between Clemson's Tajh Boyd and Florida State's Jameis Winston will highlight the Week 8 clash between the Tigers and the Seminoles.
Meanwhile in the SEC East, key injuries will continue to shape the race for a berth in the league title game in Atlanta. That process will continue on this week, namely with the Top 25 matchup between Missouri and Florida.
Then out in the SEC West Division, Auburn and Texas A&M will do battle in another Top 25 tilt that features a strong Aggie passing attack against a speedy Tiger defense.
Finally, as UCLA and Stanford square off in the Pac-12, the Bruins will likely look to a freshman running back to complement star quarterback Brett Hundley, as they look to hand the Cardinal their second straight loss.
With starting quarterback James Franklin out three to five weeks, redshirt freshman Maty Mauk will be the guy under center for Missouri.
It will be a tough first start against Florida for the former 247Sports composite 4-star. The Gators rank No. 3 in the nation in passing and total defense.
As Mizzou tries to keep its perfect 6-0 record intact while staying atop the SEC East standings, Mauk will look to connect with playmakers L'Damian Washington and Dorial Green-Beckham on the outside.
Washington, who is tied for No. 1 in the SEC with seven receiving touchdowns this season, told ESPN that he has confidence in Mauk's abilities with Franklin out of the lineup.
"I have faith in Maty Mauk," Washington said. "I know he's going to step up. He has to lead this team right now. He doesn't have a choice."
The entire SEC East has been riddled with injuries this season and Florida has been hit as hard as any team.
Already without first-string quarterback Jeff Driskel and others, the Gators learned this week that they'll be without starting running back Matt Jones for the remainder of the year. Jason Lieser of the Palm Beach Post tweeted that Jones tore his meniscus.
All the injuries will make the role of new starting quarterback Tyler Murphy that much more prevalent.
This week against Missouri, Murphy is poised for a big week. Mizzou currently ranks last in the SEC in pass defense, allowing more than 293 yards per game.
The junior hasn't eclipsed 250 yards yet in his career, but he might break that barrier against the Tigers.
Auburn's defense will be seriously challenged by the SEC's best offense when it takes on Texas A&M this week.
Against, Johnny Manziel and Co., defending the pass will be vital.
That's where AU's top defensive back Robenson Therezie will come in. The junior is tied for the SEC lead with three interceptions on the year and returned one for a touchdown two weeks ago in the Tigers' win over Mississippi.
Meanwhile, ball security has been a bit of an issue for Manziel. The reigning Heisman Trophy winner threw two crippling picks in Texas A&M's loss to Alabama and had two more costly turnovers in the Aggies' near-loss to Ole Miss.
With a strong pass rush and an opportunistic secondary, Auburn has exactly the type of defense that can give A&M's pass-happy offense fits.
Just in time for the hardest stretch of UCLA's schedule, the Bruins likely won't have the services of starting running back Jordon James.
Ryan Kartje of the Orange County Register tweeted that, according to head coach Jim Mora, James is doubtful this week against Stanford and that freshman Paul Perkins will likely start.
Perkins has been solid in a backup role for the Bruins this far, tallying 228 yards and three touchdowns, but the redshirt freshman will carry even more responsibility in a key game against Stanford.
The Cardinal are second in the Pac-12 against the run, allowing 123 yards per game.
Against the stingy Stanford defense, Perkins will be vital in taking some pressure off of star quarterback Brett Hundley.
Redshirt freshman quarterback Jameis Winston is the big-name player of the Florida State offense, but its running backs may play the biggest role in this weeks' crucial contest against Clemson.
The Tigers are just ninth in the ACC against the run but are fourth against the pass. As they look to stop Winston and the FSU passing game, big holes could open up for Devonta Freeman and the rest of the Seminole backs.
Freeman has led the bunch with 385 yards and three scores off a team-high 54 carries. Karlos Williams and James Wilder Jr. will also be important alongside Freeman.
The 'Noles play strong defense, but they'll still need to score points in bunches to keep up with Clemson.
To do that, they must be balanced.
There hasn't been a better pass rusher in the country this season than Clemson's Vic Beasley, but he's far from the only star on the CU defense.
While Beasley leads the nation with nine sacks in six games, junior linebacker Stephone Anthony has paced the Tigers with 65 tackles, including 7.5 for a loss and three sacks.
This week he'll be tasked with containing Florida State's dynamic star at quarterback, Jameis Winston, as well as the stable of Seminole rushers.
FSU ranks No. 1 in the ACC in scoring and total offense, averaging 53.6 points and 549 yards per game.
If the Tigers expect to stop the FSU attack, it'll be on Anthony to lead the CU defense.