The vast body of radiobiological data accumulated with mammalian systems in vitro and in vivo has had an enormous impact on radiotherapy. However, while quantitative, these data are essentially phenomenological, and it is only in the last decade or so that the techniques of molecular biology allow basic mechanisms to be understood. This will be illustrated by two examples, one involving cell killing and the other carcinogenesis. The identification and sequencing of repair and checkpoint control genes in the yeast S. pombe allow the mechanism of sensitivity/ resistance to radiation to be understood at the molecular level. The development of techniques to identify mutations in mismatch repair genes have made it possible to show that such mutations are associated with a wide range of human cancers and are a likely mechanism of radiation induced malignancies. Tikvah Alper would have been delighted to see the central role that micro-organisms have played in these recent developments.