Receptor-induced apoptosis is a complex signal transduction pathway involving numerous protein/protein interactions and post-transcriptional modifications. The response to death receptor stimulation varies significantly from one cell line to another and even from one cell to another within a given cell line. In this context, it is often difficult to assess whether the molecular mechanisms identified so far are sufficient to explain the rich quantitative observations now available, and to detect possible gaps in our understanding. This is precisely where computational systems biology approaches may contribute. In this chapter, we review studies done in this direction, focusing on those that provided significant insight on the functioning of this complex pathway by tightly integrating experimental and computational approaches.