Apoptosis--the cell's intrinsic program for death--plays a central role in regulation of tissue homeostasis. Accordingly, tipping the balance between cell death and proliferation in favor of cell survival can result in tumor formation. Also, killing of cancer cells by cytotoxic therapies (e.g. chemotherapy, gamma-irradiation, immunotherapy or suicide gene therapy) largely depends on intact apoptosis programs in cancer cells. To this end, it is implied that death receptor signaling contributes to the efficacy of cancer therapy. Failure to undergo apoptosis in response to anticancer therapy can therefore result in resistance. Thus, insights into the mechanisms regulating apoptosis in response to anticancer therapy and the ways in which cancer cells evade apoptosis might provide new opportunities for drug development.