We discuss here the results from our studies demonstrating that simple translocations detected by chromosome painting can be used to reconstruct radiation doses for workers exposed within the dose limits and for individuals with past exposure. To be useful, a biomarker for exposure and risk assessment should employ an end point that is highly quantitative, stable over time, and relevant to human risk. Recent advances in chromosome staining using fluorescence in situ hybridization facilitate fast and reliable measurement of simple translocations, a type of DNA damage linked both to prior clastogenic exposure and to risk. In contrast to other biomarkers available, the frequency of simple translocations in individuals exposed to whole-body radiation is stable over time postexposure, has little interindividual variability, and can be measured accurately at low frequencies.