One critical step of apoptosis is the release of mitochondrial proteins through the outer mitochondrial membrane. Recent work shows that two pro-apoptotic Bcl-2 family proteins, Bax and Bid, as well as the mitochondrion-specific lipid cardiolipin may cooperate in chemically defined liposomes to generate a protein-permeable conduit, relaunching the debate on the identity of the pore responsible for mitochondrial membrane permeabilization during apoptosis.