The p53 protein is a transcription factor activated in response to DNA-damaging agents (such as chemical or physical carcinogens) and which plays multiple role in the control of proliferation and survival of cells exposed to genotoxic stress. Recent developments in the analysis of the crystal structure of p53 help us to understand the exact role of the various domains of the protein, as well as the impact of the mutations which are frequently found in cancers. In the future, this structural approach may significantly contribute to the interpretation of the pathological consequences of p53 mutations.