Genomic instability is intrinsically linked to significant alterations in apoptosis control. Chromosomal and microsatellite instability can cause the inactivation of pro-apoptotic pathways. In addition, the inhibition of apoptosis itself can be permissive for the survival and ongoing division of cells that have failed to repair DNA double-strand breaks, experience telomere dysfunction or are in an abnormal polyploid state. Furthermore, DNA-repair proteins can regulate apoptosis. So, genomic instability and apoptosis are intimately linked phenomena, with important implications for the pathophysiology of cancer.