For decades, several compounds with radioprotective or mitigating capacity against the effects of ionizing radiation have been synthesized but their own toxicity has been the main limitation for their use. A program of synthesis and testing of radioprotectors was hence developed after the Second World War. A large number of preclinical and even clinical studies were carried out, including those on the use of some of these substances in cancer radiotherapy, intoxications, military emergencies and exposures during space flights. From those studies a radioprotector of acceptable efficacy, namely amifostine (WR-2721), arose. Despite its interesting qualities, it is far from being an ideal radioprotector due to its toxicity. The use of WR-2721 in humans has some important adverse effects, which prevent its repeated administration to achieve a sustained protective effect. An ideal radioprotector should sustain its effect for a reasonably long time and this implies that its toxicity should be low. Thus, the development of new radioprotectors, or their formulas, that act by preventing or mitigating the consequences of an exposure becomes very important. The initial idea behind our studies was to take advantage of the radioprotective capacity of amifostine when administered in a single low dose prior to radiation, but later on we continued with the administration of other substances of low toxicity that would reinforce the initial protective effect. This is how we successfully tested substances such as ethyl pyruvate and sodium butyrate, which proved to be efficient supplements for a low dose of amifostine. The results published recently by our laboratory generate a valuable antecedent about this hypothesis and open the panorama for therapeutic radiological and mitigating alternatives. The potential for clinical use of these treatments is high due to their low toxicity, which would facilitate approval for their use in humans.