Oxidative damage to DNA is the seemingly inevitable consequence of cellular metabolism. Furthermore, despite protective mechanisms, cellular levels of damage may increase under conditions of oxidative stress, arising from exposure to a variety of physical or chemical insults. Elevated levels of oxidatively damaged DNA have been measured in numerous diseases, and as a result, it has been hypothesised that such damage plays an integral role in the aetiology of that disease. This review examines the validity of this hypothesis, exploring the mechanisms by which oxidative DNA damage may lead to disease. We conclude that further validation of biomarkers of oxidative DNA damage, along with further elucidation of the role of damage in disease, may allow these biomarkers to become potentially useful clinical tools.