Advances in molecular and cellular biology are transforming our understanding of breast cancer and promise the same for radiotherapy over the next few years. At the clinical level, the molecular basis of fractionation dependency and other tumour and normal tissue responses are likely to become clearer. More importantly, they will become useful in the clinic, where molecular characterisation of the patient and tumour will start to determine therapeutic options. Although many of the fundamental processes are only amenable to study in laboratory systems, the power of array-based technologies makes it possibly to address highly relevant questions in the clinic, using functional imaging and/or tissue biopsies. To help clinical oncologists exploit these opportunities in translational research, some aspects of the molecular and cellular basis of radiotherapy are described below in their relation to breast cancer.