Deinococcus radiodurans is a model microorganism used for studies on DNA repair and antioxidation due to its extraordinary tolerance to ionizing radiation and other DNA-damaging agents. Various transcriptome analyses have revealed that hundreds of genes are induced and that many other genes are repressed during recovery of D. radiodurans following irradiation, suggesting that gene regulation is of great importance for the extreme resistance of this microorganism to ionizing radiation. In this article, we focus on some reported strategies that are employed by D. radiodurans to regulate the genes implicated in its extreme tolerance to ionizing radiation for a comprehensive understanding of the reasons this bacterium can survive such extraordinary stress. We expect this review to shed light on potential radioprotective agents and applications for use in a range of fields.