Cellular stresses such as growth factor deprivation, DNA damage, or oncogene expression can lead to cell cycle arrest or apoptotic cell death. These extreme cell responses to hostile environments are usually mediated by the p53 tumor-suppressor protein, a transcriptional activator that functions by closely regulating the expression of specific genes. More than 16 p53-inducible, apoptosis-mediating genes have been described, but it remains unclear which, if any, play a central role at this critical stage. In the September18 Science, Andreas Villunger and colleagues at the Walter and Elisa Hall Institute of Medical Research report two proteins that act as critical mediators of the apoptotic responses induced not only by p53 but also by certain drugs (Science, DOI:10.1126/science.1090072, September 18, 2003).