While the centrality of aberrant cell proliferation in cancer was widely acknowledged long ago, it is only recently that the control of cell death has been recognized as an important target in carcinogenesis. Various lines of evidence now suggest that p53 is a positive regulator of cell death, and particularly of apoptosis. Initial studies have shown that the forced overexpression of wild-type p53 can induce apoptosis in a number of cell types, mostly of hematopoietic origin. Subsequent work has confirmed that non-manipulated, endogenous wild-type p53 is required for the efficient induction of apoptotic death by a variety of signals. In particular, the lack of functional p53 interferes with the ability of ionizing radiation, and probably other types of DNA damage, to elicit apoptosis. In addition, p53 function appears to contribute to the dependence of certain cell types on survival factors, and to the induction of apoptosis by viral proteins. The decision whether the activation of wild-type p53 will lead to a growth arrest or to apoptosis, as well as the extent to which a cell is at all responsive to p53, depends on the intracellular context. DNA damage, as well as the constitutive activation of certain growth-promoting genes, are likely to be among the determinants of this context. Illegitimate cell survival may be an important consequence of the loss of p53 function, and may contribute to the carcinogenic effects of p53 inactivation.