Defect in DNA damage repair and checkpoint control is the underlying mechanism for tumorigenesis, since it allows the accumulation of multiple genetic alternations, which are essential for the initiation of tumorigenesis. This has been clearly illustrated to be the cause of several human cancer-prone syndromes and also revealed by recent human genome studies. On the other hand, defective DNA repair and checkpoint activation also make cancer cells more vulnerable for particular DNA damaging agents or inhibitors that specifically disrupt some of these checkpoint pathways. With the increasing understanding of defects in DNA repair and checkpoint control in tumorigenesis, there are extensive interests in exploring these deficiencies, especially taking advantage of the synthetic lethality concept and targeting particular DNA repair and checkpoint pathways for cancer therapy. The purpose of this conference is to bring together basic, translational and clinical investigators and discuss the current and future directions, opportunities and obstacles in the development of these anti-cancer modalities and how to best apply these concepts in clinical practice.