Barber attended Harvard University, where he studied with and was greatly influenced by the psychiatrist and writer Robert Coles. After attending graduate school at Columbia University, Barber worked for ten years with the homeless mentally ill in New York City. He worked in shelters at Bellevue and NewYork-Presbyterian Hospital, and in supportive housing programs.

In 2005, Barber published Songs from the Black Chair: A Memoir of Mental Interiors, an account of his work with the homeless and also the story of his own experiences with obsessive-compulsive disorder. The New England Journal of Medicine compared the book to William Styron’s Darkness Visible and Sylvia Nasar’s A Beautiful Mind. The title essay of Songs from the Black Chair won a 2006 Pushcart Prize, and material adapted from the book appeared in The New York Times and on National Public Radio.

In 2008, Barber published Comfortably Numb: How Psychiatry is Medicating a Nation, a critique of the over-use of psychiatric medications, particularly antidepressants, to treat and medicate everyday life problems. Comfortably Numb was a Barnes and Noble Discover Great New Writers selection, and was called "a blockbuster" by Library Journal. Salon wrote: "Compelling. In Comfortably Numb, Barber brings a street-smart perspective... Offers something several of the other books don't: practical, therapeutic alternatives to antidepressants.”

Barber wrote pieces relating to Comfortably Numb in The Washington Post, Scientific American Mind, and The Nation. In promoting the book, he appeared on Fresh Air and national television. The paperback edition of Comfortably Numb was released by Vintage Books in February, 2009.

Barber has lectured nationally and internationally at colleges, medical schools and mental health advocacy organizations. He is currently a Lecturer in Psychiatry at the Yale School of Medicine and a senior executive at The Connection, a social services agency. He has taught nonfiction writing at Wesleyan University. He lives in Connecticut with his family.