Bush played college football for the University of Southern California (USC), earned All-American honors twice, and was recognized as the top college running back. The New Orleans Saints chose him with the second overall pick of the 2006 NFL Draft. Bush won a Super Bowl title with the Saints in 2010.
Bush was the cover athlete for NCAA Football 2007. He has been known for his work with fundraising organizations and chairites, especially with Diamond Empowerment Fund, visiting Botswana and South Africa and raising money for education there.
In 2011 Bush was traded to the Miami Dolphins. On December 18th, Bush rushed for 203 yards, surpassing the 1,000 yard mark for the season, his first time as a pro.
In March 2012, Reggie became a partner and spokesperson for skincare company Barc, makers of Bump Down Razor Bump Relief. In 2013, he signed with the Detroit Lions. He was released from the Lions in 2015.