This review focuses on DNA damage caused by a variety of oxidizing, alkylating, and nitrating species, and it may play an important role in the pathophysiology of inflammation, cancer, and degenerative diseases. Infection and chronic inflammation have been recognized as important factors in carcinogenesis. Under inflammatory conditions, reactive oxygen species (ROS) and reactive nitrogen species (RNS) are generated from inflammatory and epithelial cells, and result in the formation of oxidative and nitrative DNA lesions, such as 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-nitroguanine. Cellular DNA is continuously exposed to a very high level of genotoxic stress caused by physical, chemical, and biological agents, with an estimated 10,000 modifications occurring every hour in the genetic material of each of our cells. This review highlights recent developments in the chemical biology and toxicology of 2'-deoxyribose oxidation products in DNA.