Both teams have significant injury concerns entering Saturday's high-noon showdown.
The talent behind both is not a question – Carlos Brown and Brandon Minor form a good running combination while Ryan Mallett appears to be a future star at quarterback – but the Wolverines lose many intangibles without Henne and Hart.
"Mike and Chad are great veteran players that do everything right," Michigan offensive tackle Jake Long explained. "They don't make mistakes and they give everybody emotion on both the offense and defense."
Losing either or both seniors will add even more pressure to a team that already is dealing with a three-game losing streak in the series and questions about its head coach's future.
As for the Ohio State, its top three tailbacks are all dinged up. Chris Wells (ankle, thumb), Maurice Wells (ankle) and Brandon Saine (concussion) could all play, but if any of them are out or have recurrences of their injuries, the Buckeyes will be in a precarious situation.
2. Who will win the turnover battle?
This would probably qualify as the season Ohio State should stop playing with fire in terms of turning the ball over against Michigan.
The Buckeyes are minus-5 in the last two games against the Wolverines, a deficit that makes their 2-0 record in those contests almost unthinkable.
Winning three games in a row with a negative turnover differential is a lot to ask.
Last season Michigan scored 10 points off turnovers and another lost fumble by the Buckeyes ended a drive that was on the outskirts of field goal range.
In 2005, a fumble by Maurice Wells in OSU territory stymied a strong Buckeye start and led to the Wolverines' first touchdown of the game.
Michigan later added a field goal as a result of a Troy Smith fumble.
This season Ohio State is even in turnovers while Michigan is plus-5.
3. Can Todd Boeckman rebound from his poorest outing of the season?
The Buckeye junior signal caller has gotten a lot of flack this week for a subpar performance against Illinois. His three interceptions were crucial.
Now he enters The Game as a starter for the first time with a chance to lead his team to an undisputed Big Ten title.
He admitted, though, on Monday he was not sure how he would react to a loss, simply because he had never had one as a college starter.
Not surprisingly, OSU head coach Jim Tressel expressed confidence.
"I feel good about Todd Boeckman," Tressel said. "He learns every step of the way. He's a guy that even when he errs, knows exactly why he erred, and then can do something about it, can learn from it."
4. Can the Buckeyes stop the run?
This seems like an odd question for a team that is tied for No. 1 in the Big Ten and fourth in the nation with an average of 82.7 yards allowed rushing per game, but the Buckeyes will head to Ann Arbor reeling a bit.
Illinois ripped them for more yards than any opponent in the Jim Tressel era, and two weeks before that Penn State punched some holes in the vaunted Buckeye front seven as well en route to 139 yards.
Michigan enters the game averaging 179.8 yards on the ground per contest, a figure good for the middle of the Big Ten but that likely would be better had Hart been healthy all season.
This shapes up to be an interesting matchup because neither the OSU defensive line, with three of its projected top five injured for much of the season, nor the U-M offensive front is all that strong.
The Wolverines enter the game having rushed for a total of 147 yards in their last two games. Those two Michigan opponents were Michigan State (100 yards on 30 attempts) and Wisconsin (47 on 25), teams Ohio State gashed for a 229 and 211 yards, respectively.
5. Who will win the matchups on the outside?
Fourth-quarter breakdowns against the run aside, a huge factor in the Buckeyes' loss to Illinois was the failure of the OSU secondary to control one of the nation's worst passing attacks.
Illinois quarterback Juice Williams was uncharacteristically on target with his throws, but that was helped greatly by the number of wide-open receivers on the field.
Manningham leads the Big Ten in receiving yards during conference play while Arrington (56 catches for 716 yards and six touchdowns) and Mathews (31, 299, three) are both big, physical players who are hard to match up with.
Manningham came out hot last year with three catches for 58 yards on Michigan's opening drive.
After that, he was not heard from again until the final six minutes of the fourth quarter, when he was able to work underneath a soft zone for three more grabs as Ohio State nursed an 11-point lead.
To limit Manningham, the Buckeyes opted to move Malcolm Jenkins from his normal boundary cornerback spot to the field corner, where Manningham generally lined up.
Washington was banged up and Chekwa may have still been feeling the effects of a midweek illness as both struggled against the Fighting Illini, and both need to play better to limit opponents that are far more talented than those they faced a week ago.
"They have a huge threat as far as different receivers they can throw the ball to," Jenkins said. "The entire secondary has to be on their Ps and Qs, not just one guy."
On the flip side, Ohio State attacked most acutely Michigan's lack of depth at defensive back last season. The Wolverines are not any better back there this year, but that won't matter if Brian Hartline, Brian Robiskie, Ray Small and perhaps Dane Sanzenbacher can't take advantage.