Ever since the discovery that the founding member of the Bcl-2 family of proteins contributes to tumour development by inhibiting cell survival rather than encouraging proliferation [1], interest (and controversy) in these functionally diverse homologues has raged. The Bcl-2 family of proteins participate in multiple protein-protein interactions that govern whether a cell dies in response to toxic stress. This review summarises the current knowledge of how a death stimulus culminates in the activation of Bax and Bak, the pivotal effectors of the apoptotic program, and how these critical proteins cause damage to mitochondria and the consequent demise of a cell.