Oxidative damage to DNA has been examined in many non-malignant conditions, in most cases for its utility as a marker of oxidative stress. Whilst this may prove useful, attempts to answer the question - why might oxidative damage be important in this disease? - would provide added value to the biomarker data, as well as give clues to pathogenesis and perhaps therapy. In this chapter, data from the scientific literature are considered broadly, where oxidative damage to DNA has been analysed either in tissues or in extracellular matrices, such as urine, in various groups of non-malignant disease. The lesion of primary focus is 8-hydroxy-7,8-dihydro-2'-deoxyguanosine, only because this is the most widely measured lesion. By coupling biomarker information with the characteristics of the disease and a set of general mechanisms whereby DNA oxidation may be pathogenic (retrospectively derived from the literature examined), we can ascribe pathogenic roles for DNA oxidation in various diseases. Based on available experimental evidence, for a wide range of conditions, such mechanisms would include prominent roles for the induction of mitochondrial dysfunction, promotion of cytotoxicity and modulation of inflammatory responses. Our general conclusion is that, dependent on the disease, oxidative DNA damage may be a biomarker, biohazard or both of these.