He played college football for the Iowa Hawkeyes and was selected by the Indianapolis Colts in the second round of the 2004 NFL draft.

[2] He was named NFL Defensive Player of the Year in 2007 and also played for the San Diego Chargers in his final season in 2011.

Sanders played only four games in the 2006 regular season due to a knee injury he suffered early.

With Sanders, the 2006 Colts had the second best run defense in the playoffs with only 73.3 rushing yards allowed per game.

Sanders made several key plays in the Super Bowl against the Chicago Bears, forcing a fumble from running back Cedric Benson early in the game and intercepting quarterback Rex Grossman early in the 4th quarter after cornerback Kelvin Hayden intercepted Grossman on the previous drive with both picks helping seal the 29–17 win.

He was largely responsible for shutting down Vince Young at the end of the game, clinching the victory for the Colts 22–20.

Sanders received much of the credit for the turnaround in Indy's soft defense, which saw its yards per carry average cut from 5.3 in 2006 to 3.8 in 2007.

On August 24, Sanders made his 2008 debut, along with fellow injured teammate Dwight Freeney in the week 3 preseason matchup against the Buffalo Bills.

Sanders made his return from the injury list, along with teammate Joseph Addai, for the week 9 matchup against the Patriots.

During the postgame press conference, Tony Dungy stated that Sanders was "physically, very [very] close to 100%" coming off of the ankle injury.

Sanders played in the postseason but the Colts' season was cut short by the San Diego Chargers in their wild card playoff matchup, losing 23–17.

On September 14, 2010, it was reported that Sanders could possibly miss the entire season with a torn biceps tendon.

"[citation needed] Sanders signed a one-year deal with the San Diego Chargers for the 2011 season.

[7] On September 28, 2011, he was placed on injured reserve (IR) due to swelling in his knee after playing the Patriots a couple of weeks earlier.