(A) Because the BH3 mimetic ABT-263 effectively neutralizes BCL-2 and BCL-x_L but not MCL-1, it is very effective as a single agent for malignancies in which BCL-2 or BCL-x_L is the dominant guardian restraining BAX but not those in which MCL-1 can still restrain BAX and prevent apoptosis. (B) LaBelle et al. have investigated the apoptotic potential of a hydrocarbon stapled BH3 peptide (SAHB) from the protein BIM, which broadly targets BCL-2 family proteins and can directly activate BAX as well as neutralize all its prosurvival relatives. In principle, the BIM SAHB could be more potent than a more specific BH3 mimetic, and, indeed, it proved to augment killing of hematologic tumor cells refractory to ABT-263, suggesting that such peptides might have potential as anticancer therapeutics.