Sequencing of the human genome and the acquisition of genomic data combined with advances in genomic and proteomic technologies have fueled a revolution in understanding disease. The combination of genomics and proteomics has provided a unique opportunity to diagnose, classify, and detect malignant disease, to better understand and define the behavior of specific tumors, and to provide direct and targeted therapy. Nevertheless, challenges remain, including integration and standardization of techniques and validation against accepted clinical and pathologic parameters. This article provides a summary of technologies, potential clinical applications, and challenges.