Developments in whole genome biotechnology are dramatically changing cancer drug development and the diagnosis and treatment of cancer patients. These developments have increased the opportunities for developing more effective therapeutics and for targeting them to the right patients. This can have profound benefits for patients and for the economics of health care. There are, however, serious obstacles to overcome in translating discovery of the molecular basis of cancers to the development of drugs that benefit patients. Taking advantage of the ability to diagnostically classify each cancer at the level of DNA mutations requires paradigm changes in the way drugs and combination regimens are developed, the way clinical trials are designed and analyzed and the way trial results are interpreted by the medical community, regulators and payers. Some of these issues are addressed here in the context of developing new treatments and molecular diagnostics in a manner that is practical, reliable and efficient for improving the treatment of cancer patients.