Defective apoptosis (programmed cell death) represents a major causative factor in the development and progression of cancer. The ability of tumor cells to evade engagement of apoptosis can play a significant role in their resistance to conventional therapeutic regimens. Our understanding of the complexities of apoptosis and the mechanisms evolved by tumor cells to resist engagement of cell death has focused research effort into the development of strategies designed to selectively induce apoptosis in cancer cells. This article will review the underlying mechanisms of apoptosis and the ways in which tumor cells modulate these processes to promote their survival and evaluate the efficacy of current clinical approaches aimed at exploiting these defects to selectively induce apoptosis in tumor cells.