Here I consider whether radiation-sensitive individuals might exist in the population and the potential impact of low-dose/dose-rate radiation exposure. Radiation induces DNA double-strand breaks (DSBs), which cause lethality if they are unrepaired and enhance genomic instability if they are misrepaired. DNA damage response (DDR) mechanisms play a vital role in protecting cells from the harmful effects of DSB formation. The DDR encompasses DSB repair pathways, of which DNA nonhomologous end joining is the most significant, and a signal transduction process involving ATM. Patients defective in DDR proteins have been described, and some have shown clinical radiosensitivity. However, such patients are rare and belong to defined syndromes. The critical question is whether heterozygosity or mild defects in DDR proteins confer low-dose radiosensitivity. While it is unlikely that low-dose radiation will dramatically enhance cell killing in such patients, it is possible that there could be an impact on stem cell turnover, leading to stem cell depletion with age. More importantly, it is likely that such patients could have increased misrepair of radiation damage and hence an elevated risk of radiation-induced carcinogenesis. Evidence in support of this and the potentially important genes in this context are discussed.