DNA sequence and bioinformatics technology have enabled the analysis of the cancer genome, revealing the vast genetic complexity of this disease. The patterns of somatic mutations are a rich archaeological record of the insults received by the genome that have added to our understanding of the mutagenic process. However, very few frequently mutated genes have been identified with the majority of somatic mutational events occurring infrequently. These infrequent mutations, however, have been shown to effect well-defined biological pathways that are critical in driving the development and progression of human tumours, for example the MAPK and PI3K pathways. Current cancer sequencing studies are now providing somatic mutation data for distinct tumour types and subtypes, leading to the identification of disease-specific alterations and potential therapeutic targets.