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Born in Verviers, Belgium, Sante immigrated to the United States in the early 1960s. He attended school in New York City, first at Regis High School in Manhattan and later at Columbia University from 1972 to 1976; due to several incompletes and outstanding library fines, he did not take a degree. Since 1984 he has been a full-time writer. Sante is a frequent contributor to The New York Review of Books, where he worked first in the mailroom and then as assistant to editor Barbara Epstein. Sante has written on the subjects of film, art, photography, and miscellaneous cultural phenomena as well as book reviews.
His books include Low Life: Lures and Snares of Old New York (1991), Evidence (1992), the autobiographical The Factory of Facts (1998), Walker Evans (1999), Kill All Your Darlings: Pieces 1990-2005 (2007), Folk Photography (2009), and The Other Paris (2015). He co-edited, with the writer, his former wife,Melissa Holbrook Pierson, O. K. You Mugs: Writers on Movie Actors (1998), and translated and edited Félix Fénéon's Novels in Three Lines (2007) for the New York Review Books (NYRB) series.
In the early 1980s, he wrote lyrics for the New York City-based band The Del-Byzanteens. Sante wrote the text for Take Me To The Water: Immersion Baptism In Vintage Music And Photography, a collection of historical photos of American baptismal rites, published by Dust-to-Digital in 2009.