Reaching the ambitious Cancer 2015 goal will require the application of everything in investigators' tool kits, including an openness to new ideas. Despite an unprecedented surge in researchers' understanding of what cancer cells can do, the translation of this knowledge into saving lives has been unacceptably slow. Investigators have discovered many drugs that cure artificially induced cancers in rodents, but when the substances move into human trials, they usually have rough sledding. The rodent models called on to mimic human cancers are just not measuring up. If we are going to beat cancer, we need a new path to progress.