The proteins of the BCL-2 family (pBCL-2s) are involved in the sequence of events that culminates in apoptosis, a type I cell death program. The mitochondrion is the primary site of action of pBCL-2s and represents the cross roads between the initiation and the execution phases of apoptosis. pBCL-2s are either constitutively associated with the mitochondria outer membrane (MOM) or targeted to this membrane at the onset of apoptosis. The mechanisms implicated in their targeting and activation during apoptosis is largely unknown. Recently, several pBCL-2s have been shown to interact with components of the translocase of the outer membrane (TOM), a complex responsible for the import into and across the MOM of nuclear encoded mitochondrial proteins. Here we will review the available data and discuss the possible implications of this interaction in the apoptotic programme.