Chemical modifications of DNA result from covalent interactions of genotoxic carcinogens with DNA. Persistence of certain DNA adducts can lead to mutations which can result in the development of cancer if it involves critical genes such as those involved in the regulation of cellular growth. Various analytical approaches have been used for identification and quantitation of DNA adducts but recently LC-MS/MS has proven to be an especially powerful approach. The identification and quantitation of DNA adducts in various biological samples will be outlined and strategies for identifying unknown adducts will be discussed.