Cancer cells survive despite violating rules of normal cellular behaviour that ordinarily provoke apoptosis. The blocks in apoptosis that keep cancer cells alive are therefore attractive candidates for targeted therapies. Recent studies have significantly increased our understanding of how interactions among proteins in the BCL2 family determine cell survival or death. It is now possible to systematically determine how individual cancers escape apoptosis. Such a determination can help predict not only whether cells are likely to be killed by antagonism of BCL2, but also whether they are likely to be sensitive to chemotherapy that kills by the intrinsic apoptotic pathway.