Four decades of sustained cancer research have identified many therapeutic targets including targets that induce “oncogene addiction”, the drivers of the malignant phenotype and a number of molecules critical to the bodies immune response to cancer. We are now entering an era where this effort will be largely completed for the common cancers. This represents unprecedented opportunities to translate these findings into improvement sin cancer control. Recent data from the use of BRAF inhibitors in melanoma and EML4-ALK inhibitors in non-small cell lung cancer build on the foundation developed from chronic myeloid leukaemia and gastrointestinal stromal tumours to raise the hypothesis that death rates from these cancer can be reduced by targeting these driver oncogenes.. To date effective therapeutic strategies for the oncogene-addicted cancers have been developed for less than 5% of all human cancer. We propose that developing novel strategies to target MYC and RAS driven cancers with small molecule drugs can extend this concept to a further 20-30% of human cancers. Over the next 10 years we will have a near complete catalogue of oncogenes that drive human cancer providing a novel opportunity to reduce cancer deaths. Of similar promise is the development of new immune based therapies for cancer focusing on targeting CTLA-4, PD-1 and other molecules. Early results have the potential to redefine the therapeutic landscape for cancer. Just as surgery, radiotherapy and cytotoxic chemotherapy transformed the care of cancer patients molecular biology is now poised to do the same working alongside these traditional treatments to improve survival for cancer patients.