Ultrahigh-dose rate FLASH radiotherapy (FLASH-RT) is a potentially paradigm-shifting treatment modality that holds the promise of expanding the therapeutic index for nearly any cancer. At the heart of this exciting technology comes the capability to ameliorate major normal tissue complications without compromising the efficacy of tumor killing. This combination of benefits has now been termed the FLASH effect and relies on an in vivo validation to rigorously demonstrate the absence of normal tissue toxicity. The FLASH effect occurs when the overall irradiation time is extremely short (<500 ms), and in this review we attempt to understand how FLASH-RT can kill tumors but spare normal tissues-likely the single most pressing question confronting the field today.