Purpose: To illustrate the progress in normal tissue radiation biology over the last five decades and its impact on radiotherapy.

Materials and methods: Major milestones over the last 50 years and their consequences for radiation oncology are described: The identification of clonogenic cell survival and the (target) stem cell concept, the dissociation between early and late responding tissues with regard to dose fractionation and development of the linear-quadratic model, characterisation of the effect of overall treatment time, the definition of retreatment tolerance. Current knowledge of mechanisms of radiation pathogenesis is a basis for most recent approaches for amelioration of normal tissue effects.

Results: Advances in radiobiological research in normal tissues in the last 50 years have had a major impact on radiation oncology. This includes the linear-quadratic model to adjust doses in altered fractionation protocols, and quantitation of repopulation processes to avoid toxicities in accelerated regimen. Based on new insights into the pathogenesis of normal tissue radiation effects, promising strategies for their modulation, e.g., with cytokines or by stem cell therapy, have been developed.

Conclusions: Research on radiobiology with relevant in vivo models, and relevant treatment protocols is essential for the further progress in radiation oncology.