Senator Harris Wofford, who was appointed to the position in 1991 and won a special election the same year, sought re-election to a full six-year term, but he was defeated by Republican Rick Santorum.

The polarizing Santorum took strong positions against abortion, gay rights, and affirmative action, and he even clashed with some of the traditional fixtures of the state's moderate Republican establishment.

Early in the campaign and with little statewide name recognition, Santorum made a critical error by attacking Social Security, and Wofford appeared to be in relatively safe position.

However, Santorum ran an effective grassroots campaign and specifically targeted many union Democrats who had reservations about the liberal social values advocated by many of their party's leaders.

He solidified his status by running a series of positive ads that attempted to define his character strengths and to contrast with Wofford's negative commercials.