The process of apoptosis is usually triggered by various signals that may have originated extracellularly or intracellularly  (Fig. 33.1). The apoptotic signaling initiating from an extracellular source is called an "extrinsic pathway" . The extrinsic apoptotic inducers could be small molecules, such as nitric oxide, hormones such as estrogen , or cytokines such as a tumor necrosis factor (TNF-alpha) [4-7]. The death receptor (DR) family plays the most crucial role in transducing the extracellular apoptotic signal to the cytosol apoptotic machinery . The DR family is part of the TNF-receptor superfamily and is usually activated by several cytokines called death ligands. Eight members of the DR family have been identified to date. Although the names of the DRs have varied since the initial discovery of each member, the most common names for each have now been accepted. These are DR1-TNFR1, DR2-CD95, DR3-TRAMP, DR4-TRAILR1, DR5-TRAILR2, DR-6, EDAR, and NGF-R.