Apoptosis is a physiologic process that mediates the death of selected cells [1–12]. In contrast to necrosis, which results from a strong nonspecific or toxic cell injury, apoptosis is initiated by ligand-receptor interactions that are highly regulated and tightly coupled to the phagocytosis of cells undergoing apoptosis [13–18]. Several molecules that mediate or inhibit apoptosis of immune cells have now been identified including Fas, tumor necrosis factor-receptor type 1 (TNFR1), and death domain-related (DR) DR3, DR4, DR5 and DR6 [19–25](fig. 1).

TNF-related apoptosis-inducing ligand (TRAIL) was identified as a new member of the TNF family which mediates cell death in a wide variety of malignant cell lines and primary tumor cells. There are currently four receptors identified that interact with TRAIL including DR3, DR4, DR5, DR6 and a decoy receptor DcR1/trid [20–25]. TRAIL induces two different signals, cell death mediated by caspases and gene induction mediated by nuclear factorkB (NF-B). Inhibition of TRAIL-induced activation of NF-B augments apoptosis induction by TRAIL and attenuates apoptosis resistance. Currently, TRAIL and its receptors are of major interest due to their potential roles and application in cancer therapy.