The Bcl-2 family of proteins that consists of anti-apoptotic and pro-apoptotic members determines life-or-death of a cell by controlling the release of mitochondrial apoptogenic factors, cytochrome c and apoptosis-inducing factor (AIF), that activate downstream executional phases, including the activation of death proteases called caspases. Cytochrome c release is, thus, central to apoptotic signal transduction in mammals, making study of the mechanism for cytochrome c release a major issue. Several models for cytochrome c release have been proposed, including rupture of mitochondrial outer membrane and involvement of a specific channel. Here, we provide an overview of recent findings on the role of Bcl-2 family members in the life-or-death decision of a cell.