The identification and dosimetry of DNA adducts are cornerstones of research on cancer etiology in experimental animals and humans. DNA adducts can result from exposure to exogenous chemical carcinogens or through reactions with endogenous by-products of oxidative metabolism. An important research need is high throughput methodology for quantification of any and all adducts that are present at trace amounts in DNA derived from target tissues of animals and humans. This review describes some recent progress made through applications of liquid chromatography coupled with mass spectrometry to structural characterization of unknown DNA adducts and highly sensitive quantitative analysis of target adducts.