Purpose: The search for ideal protective agents for use in a variety of radiation scenarios has continued for more than six decades. This review evaluates agents and procedures that have the potential to protect against acute and late effects of ionising radiation when administered either before or after radiation exposure.

Conclusion: Over the years, extensive experimental studies of radiation-protective agents have enhanced our knowledge of radiation physics, chemistry, and biology. However, translation of agents from animal testing to use in various scenarios, such as prophylactic adjuncts in radiotherapy or post-exposure treatments for potential victims of radiation accidents/incidents, has been slow. Nevertheless, a number of compounds are now available for use in a variety of radiation situations. These include agents approved by the U.S. Food and Drug Administration for use in reducing exposure to internal radionuclides (Prussian blue, calcium diethylenetriamene pentaacetate (DTPA) and zinc DTPA, potassium iodide) and amifostine for alleviating xerostomia associated with radiotherapy. Consensus groups have also recommended other therapies such as granulocyte colony-stimulating factor for radiation-induced neutropenia. The variety of prophylactic and therapeutic agents in the research pipeline includes those that are naturally-occurring with low toxicity, provide a long window of protection, protect normal tissue while sensitising tumours, or act via receptors and modulate biological processes such as induction of genes responsible for radioresistance. The search for agents that protect against acute and late effects of ionising radiation injury will undoubtedly continue into the future and influence other areas of radiation research.