Cancer therapy designed to kill cancer cells, work by inducing DNA double strand breaks (DSBs). These DSBs overwhelm the cells forcing them to die. Highly conserved DNA repair mechanisms protect the integrity of the genome by repairing these damages. Recently, DNA repair inhibition has emerged as a promising strategy for personalized therapy. Furthermore, employing DNA-damaging agents in combination with drugs that inhibit DNA repair pathways can have synergistic effect on eliminating cancer cells. DSBs are also introduced in the genome as part of normal physiological processes such as antibody diversification, meiotic recombination. These DSBs can sometimes get repaired in an erroneous fashion leading to human diseases including cancer. Thus, DSBs have a very important functions in physiological processes, disease initiation as well as in therapy. Studying DSBs- how they are induced, how they are repaired and how they impact the cell – is critical to have a mechanistic understanding of many fundamental processes.