Damage to DNA and RNA caused by oxidative mechanisms has been well-studied for its potential role in the development of human disease. Only recently, though, have we begun to appreciate that oxidation of the 2-deoxyribose moiety in DNA is also a determinant of the genetic toxicology of oxidative stress and inflammation, with involvement in more than just "strand breaks", such as complex DNA lesions, protein-DNA cross-links, and protein and DNA adducts. As an update to a 1992 review of 2'-deoxyribose oxidation by bleomycin and the enediynes published in Chemical Research in Toxicology [Dedon, P. C., and Goldberg, I. H. (1992) Chem. Res. Toxicol. 5, 311-332], this review focuses on recent developments in the chemical biology, bioanalytical chemistry, and genetic toxicology of 2-deoxyribose oxidation products in DNA under biologically relevant conditions.