Charlie Swanton, Group Leader at the Crick Institute, is a medical oncologist with a longstanding interest in the maintenance of genomic integrity and the implications of genomic instability for cancer development and therapy. His independent research programme has made major contributions to our understanding of the mechanisms of genome instability, and how these mechanisms play out during tumour evolution under the selective pressures that constrain cell proliferation, tumour growth, and metastasis. His work is redefining the challenges ahead in genetic diagnosis of tumour type and the application of personalised approaches to cancer medicine.