Among the 278,092 publications indexed into PubMed in 1979, a handful of articles stand out as the foundation of one of the most profound forays into the molecular basis of carcinogenesis: the discovery of the p53 tumour-suppressor protein. In the 30 years since then, understanding of p53 has progressed from obscure oncogene to key tumour-suppressor gene with clinical potential. Yet, p53 research has not followed a straight course. In this Historical Review, we describe how the 1979 discovery has shaped our view of the molecular basis of cancer, and identify some crucial steps ahead to transfer the wealth of knowledge accumulated on p53 into applications to cancer prevention and treatment.