Numerous DNA repair pathways exist to prevent the persistence of damage, and are integral to the maintenance of genome stability, and hence prevention of disease. Excised lesions arising from repair may ultimately appear in the urine where their measurement has been acknowledged to be reflective of overall oxidative stress. The development of reliable assays to measure urinary DNA lesions, such as HPLC prepurification followed by gas chromatography/mass spectrometry, offers the potential to assess whole body oxidative DNA damage. However, some studies suggest a possibility that confounding factors may contribute to urinary levels of 7,8-dihydro-8-oxoguanine (8-oxoGua) and 7,8-dihydro-8-oxo-2 -deoxyguanosine (8-oxodG). This article considers several possible sources of urinary lesions: (a) the repair of oxidatively damaged DNA; (b) a possible dietary influence; and (c) cell death. The authors conclude that data from their laboratories, along with a number of literature reports, form an argument against a contribution from cell death and diet. In the absence of these confounding factors, urinary measurements may be attributed entirely to the repair of DNA damage and suggests their possible use in studying associations between DNA repair and disease.