Two principal pathways for apoptosis initiation exist. One pathway, which is also termed the ‘extrinsic’ pathway, is mediated by death receptors, a subgroup of the TNF receptor superfamily. The second pathway, which is also referred to as the ‘intrinsic’ pathway is controlled by members of the Bcl-2 family. A long standing discussion revolves around the question of how these two pathways influence each other in regulating the decision about life or death of a cell. Here, we review our current knowledge about the interactions between these two pathways and discuss current models which could help to resolve previous apparently contradictory results.