A novel radiotherapy (RT) approach termed FLASH‑RT, which irradiates areas at ultra‑high dose rates, is of current interest to medical researchers. FLASH‑RT can maintain equivalent antitumor effects while sparing healthy tissue compared with conventional RT (CONV‑RT), which uses low dose rates. The sparing effect on healthy tissue after FLASH‑RT is known as the FLASH effect. Owing to the FLASH effect, FLASH‑RT can raise the maximum tolerable dose to control tumor growth or eradicate the tumor and provide a new strategy for clinical RT. However, definitive irradiation conditions for reproducing the FLASH effect and the biological mechanism of the FLASH effect have not yet been fully elucidated. The efficacy of FLASH‑RT is controversial despite its successful application in clinical RT. The present review recapitulates the progression of FLASH‑RT and critically comments on the hypothesis of the FLASH effect. In addition, the review expounds on the current issues with regard to the differential phenomena between in vitro and in vivo studies, and elaborates on the challenges for the application of FLASH‑RT that need to be addressed in the future.

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