Cancer research has reached an exciting phase of its evolution, as we now have an increasingly detailed molecular description of the genomic abnormalities and the biochemical pathways that drive the malignant progression of cancers. Investigation of the p53 tumour suppressor pathway, in particular, has become a key focus of current cancer research. This review describes how an increasing knowledge of the biochemistry of the p53 pathway is allowing us to develop novel strategies that rationally manipulate the function of this pathway in tumour cells for therapeutic benefit. Work in this field represents an outstanding illustration of how basic scientific research is being translated into clinical applications and the many challenges this involves.