Inheriting the position from outgoing columnist Margo Howard, she writes Slate’s Dear Prudence advice column, which appears four time per week, including one day of live chats and one day in which the letters are responded to using a video instead of text.
She also did a podcast called Manners for the Digital Age with Slate’s then-technology columnist Farhad Manjoo.
She writes a regular feature on Slate called Human Guinea Pig, in which she attempts 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. Americabeauty 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 (no relation) and Minnesota Public Radio.