Zebrafish (Danio rerio) is a bona fide vertebrate model system for understanding human diseases. It allows the transparent visualization of the effects of ionizing radiation and the convenient testing of potential radioprotectors with morpholino-modified oligonucleotides (MO) knockdown. Furthermore, various reverse and forward genetic methods are feasible to decipher novel genetic modifiers of radioprotection. Examined in the review are the radioprotective effects of the proposed radiomodifiers Nanoparticle DF-1 (C-Sixty, Inc., Houston, TX) and Amifostine (WR-2721, Ethyol), the DNA repair proteins Ku80 and ATM, as well as the transplanted hematopoietic stem cells in irradiated zebrafish. The presence of any of these sufficiently rescued the radiation-induced damages in zebrafish, while its absence resulted in mutagenic phenotypes as well as an elevation of time- and dose-dependent radiation-induced apoptosis. Radiosensitizers Flavopiridol and AG1478, both of which block progression into the radioresistant S phase of the cell cycle, have also been examined in zebrafish. Zebrafish has indeed become a favorite model system to test for radiation modifiers that can potentially be used for radiotherapeutic purposes in humans.