FLASH radiotherapy (FLASH RT) is a promising approach that uses ultra-high dose rates (UHDRs) to spare normal tissues while maintaining therapeutic efficacy on tumors. Recent research has shown that UHDRs can reduce damage to normal tissues without affecting tumor control, but challenges remain in translating this technology to clinical practice. The FLASH effect is characterized by the sparing of normal tissues and the preservation of tumor response, and it has been observed in various tissues, including lung, brain, skin, intestine, and blood. Preclinical studies have demonstrated that FLASH RT can reduce toxicity in healthy tissues and improve tumor control, particularly in models involving proton and X-ray irradiation. However, the mechanisms underlying the FLASH effect are not yet fully understood, and further research is needed to confirm the protective effects and to develop optimal technologies for delivering FLASH-compliant beams. The biological mechanisms behind the FLASH effect are complex and involve DNA damage, mitochondrial function, and other cellular processes. Current studies suggest that the FLASH effect may be influenced by factors such as oxygen tension, dose rate, and the spatial and temporal characteristics of the radiation delivery. Technological advancements are crucial for the clinical translation of FLASH RT, with a focus on developing compact and efficient accelerators capable of delivering UHDR beams. The potential of FLASH RT to revolutionize radiation oncology is significant, but further research and development are necessary to overcome the challenges and ensure its successful implementation in clinical settings.FLASH radiotherapy (FLASH RT) is a promising approach that uses ultra-high dose rates (UHDRs) to spare normal tissues while maintaining therapeutic efficacy on tumors. Recent research has shown that UHDRs can reduce damage to normal tissues without affecting tumor control, but challenges remain in translating this technology to clinical practice. The FLASH effect is characterized by the sparing of normal tissues and the preservation of tumor response, and it has been observed in various tissues, including lung, brain, skin, intestine, and blood. Preclinical studies have demonstrated that FLASH RT can reduce toxicity in healthy tissues and improve tumor control, particularly in models involving proton and X-ray irradiation. However, the mechanisms underlying the FLASH effect are not yet fully understood, and further research is needed to confirm the protective effects and to develop optimal technologies for delivering FLASH-compliant beams. The biological mechanisms behind the FLASH effect are complex and involve DNA damage, mitochondrial function, and other cellular processes. Current studies suggest that the FLASH effect may be influenced by factors such as oxygen tension, dose rate, and the spatial and temporal characteristics of the radiation delivery. Technological advancements are crucial for the clinical translation of FLASH RT, with a focus on developing compact and efficient accelerators capable of delivering UHDR beams. The potential of FLASH RT to revolutionize radiation oncology is significant, but further research and development are necessary to overcome the challenges and ensure its successful implementation in clinical settings.