In multicellular organisms, cell proliferation and death must be regulated to maintain tissue homeostasis. Many observations suggest that this regulation may be achieved, in part, by coupling the process of cell cycle progression and programmed cell death by using and controlling a shared set of factors. An argument in favor of a link between the cell cycle and apoptosis arises from the accumulated evidence that manipulation of the cell cycle may either prevent or induce an apoptotic response. This linkage has been recognized for tumor suppressor genes such as p53 and RB, the dominant oncogene, c-Myc, and several cyclin-dependent kinases (Cdks) and their regulators. These proteins that function in proliferative pathways may also act to sensitize cells to apoptosis. Indeed, unregulated cell proliferation can result in pathologic conditions including neoplasias if it is not countered by the appropriate cell death. Translating the knowledge gained by studying the connection between cell death and cell proliferation may aid in identifying novel therapies to circumvent disease progression or improve clinical outcome.