High-throughput tools for nucleic acid characterization now provide the means to conduct comprehensive analyses of all somatic alterations in the cancer genomes. Both large-scale and focused efforts have identified new targets of translational potential. The deluge of information that emerges from these genome-scale investigations has stimulated a parallel development of new analytical frameworks and tools. The complexity of somatic genomic alterations in cancer genomes also requires the development of robust methods for the interrogation of the function of genes identified by these genomics efforts. Here we provide an overview of the current state of cancer genomics, appraise the current portals and tools for accessing and analyzing cancer genomic data, and discuss emerging approaches to exploring the functions of somatically altered genes in cancer.