The GSV-R replaced Suzuki's 500 cc two-stroke V4 RGV500 which was ridden by Kenny Roberts Jr. to win the 500cc World Championship in 2000.

The first-generation GSV-R, the XRE0, was introduced in 2002 (Suzuki originally planned to wait until the following year), with regulations for that season designed for 990cc four-stroke engines in mind.

The chassis layout and wheelbase length from the 2006 GSV-R XRE4 used in the 2006 MotoGP season remained on the new model, however the fairing design had been updated to better accommodate high speed stability.

This second generation 800 cc four-stroke prototype was the most complex and technically advanced racing motorcycle Suzuki had ever produced at its time.

Along with the chassis refinements, a newly designed fairing was developed to reduce wind resistance to enhance handling characteristics.