Easier said than done, according to Tiger defensive end Andre Branch.
"No. 4, he's definitely a downhill runner," he said. "People think of him -- he might not be as big, but he's going to run at you. He's not going to try to shy away from contact at all. That's going to be a challenge."
Wilson has rushed 87 times for 516 yards and five touchdowns through four games this season.
"It's hard to slow that guy down," said Virginia Tech head coach Frank Beamer. "He's full tilt just about all the time, in about whatever he's doing. That's just the way his life is. I don't think you try to slow David Wilson down much."
As a team, the Virginia Tech rushing attack ranks 30th nationally with a 211.75 yard average, so Beamer has other places to look for carries.
The next best option behind Wilson is Josh Oglesby, who's totaled 174 yards and five touchdowns on 36 carries.
An early key for Clemson Saturday night will be to limit the big-play ability of David Wilson. (Getty Images)
Virginia Tech has come to rely on one other option for production on the ground.
Quarterback Logan Thomas, who stands 6-foot-6 and checks in at 254 pounds, has 122 yards and a score on 27 carries.
The redshirt sophomore signal caller compares favorably to last year's Heisman Trophy winner, Cam Newton.
"If you look at the size, he's not too far from Cam. He's about 10 pounds lighter. That's about it," Branch said. "He's a talented quarterback and he's a starter in the ACC, so you know he has to be some type of talent. When people compare him to Cam, until he's proved different, they've got to keep comparing him to him."
Through the first three games of the season, the Clemson run defense had given up an average of 224.67 yards. After holding Florida State to 29 in game four, Clemson's average improved to 175.75.
Since Virginia Tech has more rushing plays  than pass plays , it is within reason to believe Clemson will see plenty of Wilson, Oglesby and Thomas.
"If team says they're going to run the ball, that's on the front seven. It's our job to step up and answer that," Branch said.