Cancer is a heterogeneous disease caused largely by abnormalities of the genome and the epigenome. Typically, such abnormalities include genetic changes such as mutations and other genomic rearrangements or epigenetic changes such as aberrant DNA methylation and histone modifications that are frequently mediated by exposure to environmental or lifestyle factors. Therefore, comprehensive genetic and epigenetic analysis of cancer genomes is the most effective way to identify causative changes involved in tumorigenesis, irrespective of whether they are inherited or acquired. In this chapter, we review recent progress in the field and discuss some of the pilot studies that have already established epigenomic analysis as integral part of modern cancer research and present a major step toward personalized treatment of this disease in the future.