Three advances are dramatically changing the landscape of oncology. First, hundreds of drugs are available that inhibit targets involved in oncogenesis. Second, efforts to reclassify malignant diseases are expanding the number of orphan molecular diseases. Third, the implementation of high-throughput technologies will allow risk of relapse prediction and drug sensitivity. Patients predicted to relapse will be referred to comprehensive cancer centers where new drugs will be tested. It is anticipated that a high number of small, biology-driven clinical trials will report high sensitivity to targeted agents in rare biologically defined diseases. Drug registration and biomarker analysis needs to be revisited to avoid large phase III trials with control arms. The use of high-throughput technologies will lead to the development of virtual cells. These considerations highlight the need for developing a consortium of comprehensive cancer centers to run clinical trials in rare, molecularly-defined populations, and implement high-throughput technologies for daily practice.