Mammals bear at least five homologs of pro-survival CED-9, namely Bcl-2, Bcl-xL, Bcl-w, Mcl-1 and A1: all inhibit apoptosis during development and in response to cellular stress. They share with CED-9 at least three conserved BH (Bcl-2 homology) domains. Three of these (BH1, BH2 and BH3) fold together to form a hydrophobic groove on the pro-survival molecules (Muchmore et al., 1996). This groove is the target for ligand binding by pro-apoptotic EGL-1 or its mammalian counterparts Bik/Nbk/Blk, Bid, Bad, Hrk/DP5, Bim/Bod, Noxa, Puma/Bbc3, Bmf and Bcl-Gs. These killer proteins (BH3-only proteins) share the short BH3 domain, but no other notable sequences, with the wider Bcl-2 family (Huang and Strasser, 2000). Binding of BH3-only proteins to their cognate partners occurs through the interaction between the hydrophobic face formed by amphipathic α-helical BH3 domain and the hydrophobic groove (formed by BH1-BH3) of the pro-survival proteins (Petros et al., 2000; Sattler et al., 1997). In addition to the BH3-only proteins, the other class of pro-apoptotic Bcl-2 proteins is the multidomain Bax-like proteins. They have remarkable sequence and structural similarity to their pro-survival cousins (Suzuki et al., 2000) but function instead to promote cell death, probably at a step distinct from the BH3-only proteins.