Death receptors are cell surface receptors that transmit apoptotic signals initiated by specific ligands and play a central role in instructive apoptosis. Death receptors belong to the tumor necrosis factor receptor (TNFR) gene superfamily. Eight members of the death receptor family have been characterized so far: TNFR1 (also known as DR1, CD120a, p55 and p60), CD95 (also known as DR2, APO-1 and Fas), DR3 (also known as APO-3, LARD, TRAMP and WSL1), TRAILR1 (also known as DR4 and APO-2), TRAILR2 (also known as DR5, KILLER and TRICK2), DR6, ectodysplasin A receptor (EDAR) and nerve growth factor receptor (NGFR). These death receptors are distinguished by a cytoplasmic region of ~80 residues termed the death domain (DD). When these receptors are triggered by corresponding ligands, a number of molecules are recruited to the death domain and subsequently a signaling cascade is activated. Two types of death receptor signaling complex can be distinguished. The first group comprises the death-inducing signaling complexes (DISCs) that result in the activation of caspase-8, which plays the central role in transduction of the apoptotic signal. DISC is formed at the CD95 receptor, TRAILR1 or TRAILR2. The second group comprises the TNFR1, DR3, DR6 and EDAR. These recruit a different set of molecules, which transduce both apoptotic and survival signals.