Apoptosis, the cell’s intrinsic death program, has emerged as a key regulator in physiological growth control and regulation of tissue homeostasis. Research into the underlying mechanistic basis and its importance in disease and treatment has progressed tremendously. However, it is important to note that apoptosis is only one form of cell death and that we should not overlook the importance of other death mechanisms. The particular death pathway that is the most important determinant for cancer therapy is not necessarily that which has the fastest kinetics, as is the bias in many laboratories, but rather that which displays the most sensitive dose–response relationship. In this chapter, we argue that in many situations apoptosis is not the most important determinant of treatment response. Furthermore, we provide a summary of the different forms of cell death and discuss their contribution to cancer development and treatment response.keywordsapoptosisclonogenic survivalsenescencecancer therapy.