As a true freshman at the University of Richmond in 2004, Hightower played in all 11 games for the Spiders and carried the ball 58 times for 161 yards.

In his senior season, Hightower set school season-records with 1,924 yards and 20 touchdowns, carrying the ball 327 times (5.9 avg).

His average of 137.43 yards per game rushing led the league and ranked sixth in the nation, earning him an All-Colonial Athletic Association first-team selection.

He was considered one of the "small-school sleepers" in the 2008 NFL draft,[1] but lacked the speed of elite running back prospects.

Going into his rookie season, Hightower was behind veteran running back Edgerrin James on the Cardinals' depth chart.

In the Cardinals' season opener at the San Francisco 49ers, he had 8 carries for 13 rushing yards and a touchdown in his NFL debut.

The next week in the divisional round game against the Carolina Panthers, Hightower had 17 carries for 76-rushing yards and scored on a 3-yard touchdown reception, helping his team win 33–13.

Hightower ended up carrying the ball 11 times for 33 rushing yards and caught a game-winning 8-yard touchdown reception to seal the victory 32–25.

On October 18, 2009, he ran for 32-yards on 13 carries and scored a rushing touchdown, while also accounting for 26-yards on 4 receptions in a 27–3 victory over the Seattle Seahawks.

In a Week 11 contest against the St. Louis Rams, Hightower carried the ball 14 times for 110 rushing yards as Arizona won 21–13.

In the NFC Wild Card game against the Green Bay Packers, Hightower had only 7 carries for 19 yards but scored a touchdown as they won 51–45.

Hightower began the 2010 season returning as the Cardinals' starting running back ahead of Beanie Wells and Ryan Torain.

[5] Hightower was traded on July 31, 2011, to the Washington Redskins in exchange for defensive end Vonnie Holliday and a sixth round draft pick in 2012.

Hightower was named the Redskins starting running back in the season opener and had a career-high 25 carries for 72 rushing yards and scored a touchdown in a 28–14 victory over the New York Giants.

[17] He was re-signed a second time to the Saints' active roster on November 2 after Khiry Robinson was placed on the team's injured reserve.

[19] He entered the 2016 season as the primary backup to Mark Ingram II after the Saints had released C. J. Spiller during the offseason.

On December 18, 2016, Hightower recorded 11 carries for 37 rushing yards and a season-high two touchdowns in a 48–41 victory over the Arizona Cardinals, his former team.