The crucial role of mitochondria in the initiation of apoptosis is well established. The metabolic consequences of mitochondrial membrane permeabilization as well as the leakage of apoptogenic factors normally confined to mitochondria determines the catabolic features of cell death. Here we attempt to summarize the current view of the mechanisms that lead to the efflux of many proteins from mitochondria during apoptosis and the role played by Bcl-2 family proteins in these events.