In July 2017, the 17th International p53 Workshop was held in Singapore. With an attendance of over 300 scientists from all over the world, the meeting was an outstanding success and many new observations about the p53 pathway were discussed for the first time. The enthusiasm to gather these insights into a form that would be available to the whole community led us and the editors of Journal of Molecular Cell Biology to design a special issue of the journal composed of articles and commentaries from some of the key contributors to the meeting. As is usual, deadlines have to stretch a little, but in the end, 14 excellent papers have been assembled and many cited papers that have literally been published only in the last few months ensuring a remarkably up to date coverage of the field. We have had to spilt the contributions over two volumes in order to accommodate them within the journal, but there is also a natural split as one area of intense study is the regulation of the wild-type protein, while the other strongly developing area is the growing realization that the point-mutant proteins expressed at high levels in many human cancers are acting as driver oncoproteins. The hope is that the intense study of both areas will lead to new insights into how to prevent, diagnose, and treat cancer.