A self described "liberal Republican", Saletan came out strongly against the re-election of George W. Bush.
Saletan has written several articles about bioethics and sexual ethics, criticizing what he sees as homophobia within the Roman Catholic Church.
Liberal William Saletan Announces Plan to ‘Purge’ Christians
In an article titled, “Purge the Bigots,” Slate writer William Saletan penned these chilling words: “Some of my colleagues are celebrating. They call Eich a bigot who got what he deserved. I agree. But let’s not stop here. If we’re serious about enforcing the new standard, thousands of other employees who donated to the same anti-gay ballot measure must be punished.
“More than 35,000 people gave money to the campaign for Proposition 8, the 2008 ballot measure that declared, ‘Only marriage between a man and a woman is valid or recognized in California,’” he continued. “Why do these bigots still have jobs? Let’s go get them.”