A genomic era of cancer studies is developing rapidly, fueled by the emergence of next-generation sequencing technologies that provide exquisite sensitivity and resolution. This article discusses several areas within cancer genomics that are being transformed by the application of new technology, and in the process are dramatically expanding our understanding of this disease. Although, we anticipate that there will be many exciting discoveries in the near future, the ultimate success of these endeavors rests on our ability to translate what is learned into better diagnosis, treatment and prevention of cancer.