Melvin Gordon scored his fourth TD of the season in Week 3 and gets a premium matchup Sunday at home against a Saints defense allowing a league-worst 149.3 rushing yards per game so far.
Ezekiel Elliott rushed for 140 yards on 30 carries last week, and will get the ball early and often again facing the 49ers' 23rd-ranked run defense Sunday.
DeMarco Murray, more than anyone else on the Titans' roster, is a sure play in Week 4 against the Houston Texans, who rank 27th in rushing defense.
Jeremy Hill has a Thursday matchup against a Dolphins’ defense that allowed 123 rushing yards to LaGarrette Blount in Week 2 and then 148 yards to the Browns’ duo of Isaiah Crowell and Duke Johnson last week.
Isaiah Crowell has a Sunday contest against a Washington defense that has allowed six touchdowns to running backs through three games this season.
Jordan Howard has an inviting matchup against a Lions defense which is allowing a league-high 5.1 yards per carry, and would see a boost in appeal should Jeremy Langford (ankle) miss the contest.
Lamar Miller has been Houston's workhorse through the first three games, ranking second among running backs with 74 carries, and will carry the load once again in Week 4 against the Tennessee Titans, who rank 17th in rushing defense.
Todd Gurley should be able to follow last week's two-touchdown performance with another strong game Sunday against a Cardinals defense that ranks 29th against the run.
LeSean McCoy is coming off his best game of the young season, though he'll be facing a New England Patriots defense in Week 4 that allows just 90.3 yards per game on the ground.
Theo Riddick managed only nine yards on 10 carries last week, and has more appeal where his seven catches add to his value heading into a matchup against a Bears defense that ranks 31st against the run, allowing 142.7 yards per game.
C.J. Anderson had a quiet Week 3 as the Broncos' passing game took the lead, but he should be more involved Sunday against a Buccaneers defense that just gave up two TDs to Todd Gurley.
Jerick McKinnon out-touched Matt Asiata 17-to-7 in the team's first game without Adrian Peterson, but faces a stern test Monday night against a Giants' fifth-ranked rush defense that is allowing only 77.3 yards per game.
Charles Sims will be a strong play for the Bucs on Sunday against the Broncos after they allowed 143 yards and 4.9 yards per carry to the Bengals last weekend.
Giovani Bernard will take on the Dolphins on Thursday night after catching 16 passes for 141 yards and a touchdown in three games this season.
Alfred Morris has vultured a couple touchdowns, but Ezekiel Elliott is still the clear go-to running back in Dallas heading into Sunday's plus matchup with the 49ers.
Dwayne Washington is the best bet in a limited rushing offense, and faces a Bears defense that ranks second-to-last against the run, allowing 142.7 yards per game
Fozzy Whittaker will look for more than five carries as he’s just a week removed from his 100-yard performance against the 49ers for Sunday’s divisional matchup against the Falcons, who allowed the sixth-most fantasy points to opposing running backs in 2015.
Mark Ingram’s averaging just 12 carries per game, but still managed more than 100 total yards and a score despite just 19 touches on Monday night, and he'll try to build on his solid performance Sunday against the Chargers.
Le’Veon Bell will make his season debut Sunday against the Chiefs, a team he rushed for 121 yards against last season in a game that backup quarterback Landry Jones started.
Devonta Freeman broke the 200-yard barrier in total yards (152 on the ground, 55 as a receiver, plus a touchdown for good measure) but saw three touchdowns swiped by Tevin Coleman on the ground, and he'll look to continue his success Sunday against the Panthers.
LeGarrette Blount will once again be the focal point of the New England offense without Tom Brady, though he'll face a Buffalo Bills defense allowing just 98 yards per game on the ground.
Carlos Hyde has scored four times through three weeks, and is likely to find pay dirt Sunday in what promises to be a run-heavy game against Dallas.
Duke Johnson will face Washington on Sunday where he’ll look to have a fourth straight game with at least 50 total yards.
David Johnson's well-rounded game makes him likely to have another strong performance Sunday against a Rams team that ranks 18th in total defense.
Matt Jones is likely to take a back seat to Washington's passing game Sunday against a Browns defense that ranks 18th against the run and 25th against the pass.
Tevin Coleman rushed for another three touchdowns against the Saints, which gives him plenty of value Sunday against the Panthers, even as he gets consistently (albeit slightly) out-touched by Devonta Freeman.
Cameron Artis-Payne averaged 3.9 yards per carry against the Vikings and should find more room to run Sunday against the Falcons, who allowed the sixth-most fantasy points per game to opposing running backs last season.
Orlean Darkwa could play a major role on Monday Night Football in Minnesota with Rashad Jennings (thumb) questionable and Shane Vereen (triceps) done for the year.
The Colts' offense was at its best when they worked a heavy ground attack behind Frank Gore last week, but they're not always in a position to do that. Week 4's opponent, the Jacksonville Jaguars, offers potential for Gore as the Jags rank 20th in rushing defense.
Jeremy Langford continues to lose snaps to Jordan Howard, and is dealing with an ankle injury heading into an inviting matchup against a Lions defense allowing a league-high 5.1 yards per carry.
James White has been underwhelming in the Dion Lewis role and will likely continue to be underutilized Sunday against the Bills.
Powell had 10 touches for 71 yards last weekend, though he'll likely find little room to roam against a Seattle defense allowing a league-low 250.3 yards per game.
The Jaguars' offensive line has not been very good for the running game, making T.J. Yeldon an iffy play in Week 4 against the Indianapolis Colts, who rank 13th in rushing defense.
Derrick Henry is getting more and more playing time but remains the second back behind DeMarco Murray in Tennessee's run-first offense. He could vulture a red-zone touchdown in Week 4 against the Houston Texans.
Chris Ivory made his season debut last week, gaining just 14 yards on 12 carries behind an offensive line that hasn't opened many holes in 2016. We'll see if one more week removed from his medical condition makes for better production in Week 4 against the Indianapolis Colts, who rank 13th in rushing defense.
Rashad Jennings is questionable for Monday's game in Minnesota with a thumb injury, but would be in line for a solid workload if he suited up with Shane Vereen (triceps) done for the year.
Jamaal Charles was held out again in Week 3 as he continues his recovery from knee surgery, but could be ready to make his season debut Sunday against a Steelers defense that gave up over 240 yards from scrimmage to Eagles RBs last week.
Spencer Ware rushed for 75 yards in Week 3's win over the Jets, but with Jamaal Charles seemingly poised to return to the lineup Sunday, Ware's touches will shrink considerably.
Latavius Murray scored for the third straight week against the Titans but was otherwise quiet, and now faces a Ravens defense that ranks in rushing yards allowed so far at 86.0 per game.
Justin Forsett will face the Raiders in Week 4 after posting just 113 total yards over three games this season.
Christine Michael seized the starting job with a two-touchdown performance last week, but expectations should be tempered Sunday against a Jets defense that allows just 71.7 rushing yards per game.
Matt Forte was held in check last week, and the Jets will likely be playing from behind against a stout Seattle run defense allowing just 87.7 yards per game on the ground.
Isaiah Pead had five carries in last weekend's game, though Kenyan Drake had the most carries in the absence of Arian Foster, while Jay Ajayi scored a rushing touchdown, and he'll try to earn more work Thursday against the Bengals.
Doug Martin is unlikely to play for his second-straight game against the Broncos stingy run defense.
Matt Asiata was out-snapped 36-to-19 by Jerick McKinnon, receiving only seven touches in the team's first game without Adrian Peterson, and will need goal line work to provide value Monday night against the Giants fifth-ranked rush defense.
Alfred Blue played just two snaps on the final drive of Houston's loss to the Patriots in Week 3 and will continue to take a heavily subordinate role to Lamar Miller in Week 4 against the Tennessee Titans.
Jonathan Grimes had his most use of the season last week, primarily in the passing game, but like the rest of the Houston running backs, he's buried behind starter Lamar Miller as the Texans prepare for a Week 4 home game against the Tennessee Titans.
Kenyan Drake actually had the most touches out of the backfield last week, though Jay Ajayi scored a touchdown in the absence of Arian Foster, and a timeshare looms with Isaiah Pead in the mix as well as he faces the Bengals on Thursday night.
Antonio Andrews is buried on the depth chart behind DeMarco Murray and Derrick Henry entering Week 4 against the Houston Texans.
Jay Ajayi had a touchdown run in the absence of Arian Foster, though Kenyan Drake actually had more touches out of the backfield, and a timeshare looms with Isaiah Pead in the mix as well when he faces the Bengals on Thursday.