For decades, the main cellular target for radiation induced damage was thought to be the DNA molecule. This view has been challenged by data indicating that in order to increase survival, the cells must protect their proteins, which in turn repair the damage in the DNA. An important part of protection of proteins (but not DNA) against the detrimental effects of reactive oxygen species (ROS), which are the main mechanism of radiation toxicity, is played by non-enzymatic complexes of manganese ions and small organic metabolites. These complexes were shown to protect the proteins from oxidation in vitro and also increased radiation survival in mice. An application of the synthetically reconstituted protective mixture with manganese was shown to preserve the immunogenicity of viral and bacterial epitopes at radiation doses far above those necessary to kill the microorganisms, thus opening a possibility for a quick whole-organism vaccine production. The intracellular manganese content and the nature of complexes it forms (both measurable by electron paramagnetic resonance) were shown to correlate with radiosensitivity in bacteria, archaea, fungi and human cells. An association was also found between total cellular manganese contents and their variation, and clinically inferred radioresponsiveness in different tumor cells, a finding that may be useful for more precise radiodosages and improved treatment of cancer patients.