The Democrat nominee who had never run for public office and was expected to face an uphill battle in the general election, especially in a state that has not elected a Democrat statewide since 1994 and against a historically popular Hutchison. Since neither Radnofsky nor her main opponent, Gene Kelly, had received a majority of votes in the Democratic primary, a runoff was held on April 11, 2006, which Radnofsky won. Radnofsky's campaign platform is available on her website.  Scott Lanier Jameson won the Libertarian Party nomination at the party's state convention on June 10, 2006, defeating Timothy Wade and Ray Salinas. Arthur W. Loux, a Roman Forest City Councilman and a member of the Minutemen, was running as an independent.
Hutchison co-sponsored legislation supporting the creation of a constitutional amendment that would limit terms for senators, but had been quoted saying that she would only leave after two terms if such a law applied to all senators. After deciding not to challenge Governor Rick Perry this year, as had been widely speculated, Hutchison was running for a third term.
She had no opposition in the 2006 Republican primary, and had approval ratings in the 60 percent range going into the General Election , although they have been slipping rapidly.