Radioactive caries is the most common complication of head and neck cancer after radiotherapy. It is a rapidly progressing and widespread destructive disease of tooth tissue after radiotherapy. It is currently believed that salivary gland dysfunction and direct damage to teeth by radiation are the main pathogenic factors of radiation caries. In this paper, the pathogenesis of radiation caries, especially the effect of radiotherapy on oral caries-related microorganisms, are reviewed, and future research directions are proposed. Existing research has revealed that the structures of oral microorganisms change significantly after radiotherapy. The number and proportion of some dental caries-related microorganisms such as Streptococcus mutans, Lactobacillus lactis and Candida albicans increased, and their virulence increased. This indicated that the changes in oral microorganisms caused by radiotherapy played an important role in radioactive caries.