There are lots of pivotal division matchups in Week Four of the NFL this weekend, and like always who is in and who is out could make all the difference.

Several other key players could make a return for teams that need an early boost this season to avoid any talk of missing the playoffs.

San Francisco 49ers (1-2) at St. Louis Rams (1-2)

In this NFC West clash, both teams are in need of a win to right their respective ships. The 49ers are already missing All-Pro Aldon Smith for an indefinite period of time, while corner Nnamdi Asomugha, right tackle Anthony Davis, tight end Vernon Davis, and linebacker Patrick Willis are listed as questionable.

The Rams appear to be more at full strength than San Francisco. Right tackle Rodgers Staffold, and second-string defensive end Willie Hayes are listed as out, but no players are questionable.

Chicago Bears (3-0)  at Detroit Lions (2-1)

The Lions can take a commanding lead in the NFC North with their second division victory, but meet a Chicago squad fresh off a 17-point rout in Week Three.

The Lions are currently banged up on both sides of the ball, but running back Reggie Bush was a full participant in Wednesday’s practice, an excellent sign for the Lions, and a bad one for the Bears. However top receiver Calvin Johnson, safety Louis Delmas, and guard Rob Sims did not participate.

Chicago lost defensive tackle Henry Melton to a season-ending ACL tear last week and are reportedly trying to plug the hole with free agents Landon Cohen and Daniel Muir, or promote end Cheta Ozougwu from the practice squad.

Top corner Charles Tillman also sat out practice on Wednesday with knee and groin ailments.

Cincinnati Bengals (2-1) at Cleveland Browns (1-2)

The Bengals have won two straight, but their secondary appears to be dragging along. Corners Leon Hall and Dre Kirkpatrick, along with safety Reggie Nelson, and guard Mike Pollak were all on the sidelines during practice on Wednesday. Corner Terence Newman was also limited.

Meanwhile Cleveland can start their own winning streak, but their defensive frontline may lack some depth. Second string defensive end Billy Winn was out with a quad injury, and so was outside linebacker Quentin Groves. First string outside linebacker Jabaal Sheard was also out with a knee injury.

Indianapolis Colts (2-1) at Jacksonville Jaguars (0-3)

With Houston taking on Seattle, the Colts could take control of the AFC South against the reeling Jags. Indianapolis starting center Samson Satele was limited on Wednesday with an elbow injury, just as the Colts offensive line gave up only one sack in Week One. However most of the Colts worries should revolve around the defense, with leading safeties Antoine Bethea and LaRon Landry, and d-tackle Ricky Jean Francois sitting out on Wednesday.

With injuries on both sides of the ball, Jacksonville’s chances of earning their first win may be in doubt. Receiver Stephen Burton and safety Dwight Lowery each have head injuries, and running back Maurice Jones-Drew has an ankle ailment. All three did not practice on Wednesday.

Baltimore Ravens (2-1) at Buffalo Bills (1-2)

The defending Super Bowl champs already listed receiver Jacoby Jones as out with a knee injury, while receiver Marlon Brown and nose tackle Terrence Cody highlight five Ravens who sat out of practice. Running back Shaun Draughn has an ankle injury as well, further depleting the Ravens running game. However Ray Rice did practice in a limited role.

Buffalo’s 19th ranked secondary has a few bumps and bruises. Corners Ron Brooks, Stephon Gilmore and Leodis McKelvin did not participate in practice, and star safety Jarius Byrd was limited. Top defensive end Mario Williams and running back C.J. Spiller have both gone on record to say they expect to be ready for Sunday.

New York Jets (2-1) at Tennessee Titans (2-1)

The Jets defense is humming, though defensive tackle Sheldon Richardson was held out of practice on Wednesday with a shoulder knock. While linebacker Quinton Coples, defensive tackle Kenrick Ellis, and rookie corner Dee Milliner were limited. Running back Chris Ivory is also nursing a hamstring injury.

The Titans are coming off their first big win of the season, but linebacker Patrick Bailey and defensive tackle Sammie Hill were out on Wednesday. However linebacker Zaviar Gooden was a full participant and linebacker Moise Fokou was limited with a neck injury.

Arizona Cardinals (1-2) at Tampa Bay Buccaneers (0-3)

The Cardinals can breathe a sigh of relief as top receiver Larry Fitzgerald played in a full practice for the first time in weeks, and the same goes for defensive end Ronald Talley. The secondary could miss safety Rashad Johnson due to a severed finger, and linebacker Kevin Minter and defensive tackle Dan Williams were out on Wednesday.

The Bucs have already ruled out corner Michael Adams, while guard Gabe Carimi sat out with an illness, and defensive tackles Gary Gibson and Derek Landri were also on the sidelines. Still, defensive tackle Gerald McCory and corner Rashaan Melvin were full participants.