This issue of Recent Results in Cancer Research presents a comprehensive review of current understanding of chromosomal instability in cancer and of strategies to use this information for better treatment of patients with cancer. Cancer is a disease of the chromosomes, and chromosomal instability in cancer disrupts gene function by either inactivating tumor suppressor genes or activating growth-promoting oncogenes. The chromosomal basis for these aberrations is either translocations, which change the integrity of genes, or abnormal numbers of chromosomes, a condition referred to as aneuploidy, which results in abnormal gene expression levels. Such structural or numerical chromosomal aberrations are specific for distinct tumor entities. The degree of chromosomal instability and the degree of intratumor heterogeneity have profound consequences for disease outcome and for therapeutic stratification.