Apoptosis, the cell's intrinsic program to death, plays a central role in physiological growth control and regulation of tissue homeostasis. Tipping the balance between cell death and proliferation in favor of cell survival may result in tumor formation. Also, killing of cancer cells by cytotoxic therapies currently used for treatment of cancer, for example, chemotherapy, gamma-irradiation, immunotherapy, or suicide gene therapy, largely depends on activation of apoptosis programs in cancer cells. Accordingly, failure to undergo apoptosis in response to anticancer therapy may result in cancer resistance. Further insights into the mechanisms regulating apoptosis in response to anticancer therapy and how cancer cells evade cell death may provide novel opportunities for drug development.