An editorial notes that imatinib is highly successful at controlling the disease in the long term, but few, if any, patients would be considered to be “cured” (in a stable remission and not taking any therapy). It discusses the development of imatinib and how it has fundamentally altered the field of oncology, whilst noting the inherent genetic instability of many cancers also facilitates the development of resistance to interventions. It highlights the need to learn how to combine therapies that have different targets, to identify patients who are likely to have a response, and to define mechanisms of resistance.