The p53 tumour-suppressor gene encodes a transcription factor which plays a central role in controlling oncogenic development in mouse and humans. Mice which over-express mutant p53 transgenes or have a homozygous deletion of the p53 gene show a high frequency of spontaneous tumour development. This review will focus on recent developments using these transgenic and null mice which suggest that p53 is important in maintaining genomic stability, and is a critical component in the cellular response to ionizing radiation.