In 2006 outgoing columnist Margo Howard turned Slates "Dear Prudence" advice column over to Yoffe. The column appears four times per week, including one day of live chats and one day in which the letters are responded to using a video instead of text. In November 2015, Yoffe published her last "Dear Prudence" column, and has since been replaced by Daniel M. Lavery, co-founder of The Toast. Yoffe also hosted a podcast called "Manners for the Digital Age" with Slates then-technology columnist Farhad Manjoo. She wrote a regular feature on Slate called "Human Guinea Pig", in which she attempted unusual activities or hobbies. For "Human Guinea Pig", she has tried hypnosis, and taken a vow of silence. She has become a street performer, a nude model for an art class, and a contestant in the Mrs. America beauty pageant. In June 2005, Bloomsbury published Yoffe's What the Dog Did: Tales from a Formerly Reluctant Dog Owner. That year it was named Best Book of the Year by Dogwise, and selected as the Best General Interest Dog Book by the Dog Writers Association of America. She has been a guest on The Colbert Report twice. She discussed her experiences as Slate's "Human Guinea Pig", and an article about narcissistic personality disorder. She has been a guest on numerous radio programs, including The Emily Rooney Show and Minnesota Public Radio. Yoffe has written pieces about the worldwide disappearance of frogs and the crash of Air Florida Flight 90 for The New York Times Magazine. She has written op-eds for The Washington Post on global warming, motherhood, and politics.
Yoffe has written extensively about campus sexual assault and the Obama administration’s effort to end it, describing the administration’s reforms of Title IX – the United States federal law prohibiting sex discrimination in federally-funded education programs – as a worthy goal that went awry. Her article in Slate, “The College Rape Overcorrection” was a National Magazine Award finalist in Public Service in 2015. She wrote a series on campus sexual assault for The Atlantic on due process, junk science, and racial disparities. She has praised #MeToo, but expressed concerns about overreach. She wrote about “The Problem With #BelieveSurvivors”, the consequences of Al Franken’s resignation from the Senate, and the dangers of "endlessly expand the categories of victim and perpetrator."
