Interactions between ionizing radiation and living organisms may produce genome and epigenetic damage, and disturbances of signal molecules, cell proteins and biological pathways which can be repaired or can be become permanent and represent a health risk. In order to follow the complexity of the biological response to radiation it is necessary to apply several biomarkers simultaneously. Thanks to rapid accumulation of data from -omics techniques, biomonitoring and biodosimetry after environmental, accidental or occupational exposure to ionizing radiation was able to develop from assessment at group level to individual level. Interpretation of the results of biomonitoring using both new and old biomarkers gives insight into age and gender differences in the pathways involved in radiation-related carcinogenesis, including deviations of signaling. There is still a knowledge gap in transgenerational and developmental biodosimetry, especially for the pubertal period. Analysis of the available studies on biomonitoring of populations exposed to ionizing radiation show clearly that, in investigation of the complex responses of living organisms, biomarkers have significant advantages when compared with other physical measurements and calculations of health risk. Introduction of systems biology as a tool in the future will enable improvement of radiation protection legislation and individual life-long health risk assessment related to exposure to ionizing radiation. Development and introduction of methods that will enable reliable biodosimetry in cases of accidental overexposure of large populations are in progress.