The response to ionising radiation, in terms of level of cell killing, depends on a number of factors that may be grouped into those that are genetically controlled, radiation quality and dosage, and environmental factors. There is a range of genetically controlled cellular properties such as stage of differentiation, mutations in specific genes (such as p53 and bcl-2) and stage of transformation that will determine the ability of the target cell to enter apoptosis. The so-called normal cells, are usually more radiosensitive and the majority of the cell population will enter into an apoptotic death. However, in response to high doses of ionising radiation and complex DNA damage as produced by high-LET radiation, an increased fraction of these cells will die by necrosis. There are several examples of environmental factors with relevance for the combined action of radiation and xenobiotics on carcinogenesis and in tumour therapy. In the case of normal cells, agents such as growth factors and tumour promoters, may decrease radiosensitivity. For certain type of tumour cells, radiation sensitivity can be increased in the presence of agents such as hormones, and the cells may die an apoptotic death. Removal of heavily compromised cells is essential to prevent a potential spreading of mutated clones. However, if apoptosis is inhibited (e.g., by tumour promoter), an increased fraction of damaged cells carrying genotoxic lesions may survive. This would significantly increase the risk of proliferation of precancerous cells. As discussed above, it is probably incorrect to make predictions about relative radiosensitivity based solely on mode of death. Intrinsic characteristics deriving from the cell type of origin of a line may be more important in determining radiosensitivity. The rapidly increasing knowledge about the process of radiation induced apoptosis has opened new frontiers in radiation biology, genetic toxicology, and cancer therapy and strongly motivates further research in this field.