Houston has already locked up the division, and although Indy is feeling confident after besting the Titans last week for win No. 1, the game's only purpose is to see the development of its rookies.
So here are a couple of rookies from each team to look for.
Plagued by numerous injuries this season, the Houston Texans have fought through them and still managed to win the AFC South.
Currently holding a 10-4 record, they've counted on rookie quarterback TJ Yates since late November and he's proved to be worth the investment.
Even without wide receiver Andre Johnson, Yates has managed games superbly; he led an impressive game-winning drive against the Bengals in Cincinnati.
However, Yates had his rookie moment last week against Carolina, throwing two picks. It was definitely a learning moment for the young quarterback; how he responds at Indianapolis will be telling.
That said, the Colts do have a defense and Houston's rushing attack will be Yates' safety net. Don't expect any more than 20-25 attempts from Yates on Thursday; gradually acclimating him under center is important.
Watch how Yates goes through his progressions. If it occurs quite often, he displays poise in the pocket while feeling the rush.
After a down game in week 15, his week 16 intangibles with shortened preparation will reveal quite a bit.
It's no secret that the Houston Texans' defense has vastly improved since last season. Now, there are a lot of players to dish the credit around to, but one to really watch for is defensive end JJ Watt.
Watt is a 6-foot-5, 290-pound force coming off the edge, and is great at causing pressure while being a sure tackler. On the year, he as accounted for 4.5 sacks, 50 tackles and two fumble recoveries.
Much like everyone else on the Texans' defense, Watt has significantly contributed to their success and improvement. Against the Colts, his presence on the outside must draw attention because Indy has the potential to run the ball well and they have reliable receiving targets.
Therefore, not only can we expect Watt to pass rush and dip inside on occasion to stop the run, but he has the size and wherewithal to drop into coverage.
We know the Colts like those slip screens and underneath crossing patterns, so having Watt help to shield those off will limit their options and production.
Whether it's Watt, Brooks Reed, Connor Barwin, or Brian Cushing, Colts rookie offensive tackle Anthony Castonzo must play flawless in week 16.
Houston has an aggressive defense with four guys who can rush the quarterback both inside and out.
If Castonzo can't wall off the edge, Indy's offense will struggle throughout; this holds especially true in the ground game.
It's the one area where the Colts have had success on offense this season. That being said, however, against this defense you can't just pound the rock inside all day.
Using the passing game to setup draws and quick tosses will be imperative.
As for Castonzo, the better the pass protection, the better the odds of draws and screens working. The Colts are good enough to just attack Houston straight up. They need to manipulate and deceive to some extent.
Unfortunately, that won't happen if Castonzo fails to reduce the pass rush. There, the screens, draws and tosses won't have time to develop as defenders bombard the backfield all game long.
Nonetheless, if Castanzo can dominate anyone blitzing on his side, it's similar to a cornerback covering half the field on defense.
No one has success to that side, and it provides them with an extreme advantage. There, the Colts' offense would then be able to take over the game.
If the Colts want any shot at shutting down the Texans' ground game, utilizing cornerback Chris Rucker's versatility is key.
For one, we know the Texans won't try to throw the ball much with rookie quarterback Yates under center, although he has proven the ability to be clutch.
That being said, disguising blitzes with Rucker by showing press coverage, but then darting off the edge and into the backfield will suffice.
With Yates getting acclimated to being under center and the Colts literally having nothing to lose, why not try to confuse the offense?
Indy does have a solid pass rush on the defensive line, but that won't be enough to slow Houston's rushing attack.
Last week, Rucker recorded 11 tackles against Tennessee, so it's clear that his presence in the box will assist in stopping Arian Foster and Ben Tate.
The Colts need to take risks if they want to win this game.
Using Rucker on blitzes, inside the box and consistently in press/zone coverage will allow others to be better positioned to make plays.
Rucker is the x-factor of the Colts' defense; it'll be interesting to see how he produces against the AFC South champions.