Apoptosis is a genetically controlled form of cell death that is important for normal development and tissue homeostasis. Senescence produces “genetic death” in that the senescent cell is incapable of further propagation. Both processes are frequently disrupted in cancer cells, implying that each can limit tumor development. Moreover, radiation and many chemotherapeutic agents can induce either apoptosis or senescence, raising the possibility that the integrity of these programmed responses influences the outcome of cancer therapy in patients. The goal of our research is to understand how cancer genes control apoptosis and senescence in normal cells, and how mutations that disrupt these processes impact tumor development and therapy. Our approach emphasizes genetics, and we have increasingly relied on new types of animal models and gene manipulation technologies to study tumor development and cancer therapy in vivo.